Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,mar...Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.展开更多
Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored...Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.展开更多
BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or to...BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.展开更多
Bone sialoprotein(BSP)is an important non-collagen extracellular matrix protein(EMC)that promotes bone formation and induces bone resorption.BSP is secreted by odontoblasts,it plays an important role in cementum,alveo...Bone sialoprotein(BSP)is an important non-collagen extracellular matrix protein(EMC)that promotes bone formation and induces bone resorption.BSP is secreted by odontoblasts,it plays an important role in cementum,alveolar bone formation and mineralization,and periodontal function.Bone resorption is controlled by a complex molecular network,and BSP can promote osteoclast differentiation and bone resorption.It is also associated with the metastasis of a range of malignancies.Osteoclasts(OC)are thought to be the only cells involved in bone resorption and play an important role in bone formation and late developmental remodeling.Osteoporosis and periodontal disease are caused by excessive bone resorption.This article will summarize the osteoclasts differentiation,the biological function of bone resorption,and explore the progress of the prevention and treatment of the related bone resorption diseases such as osteoporosis and periodontal disease through the regulation of osteoclasts.展开更多
Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) ra...Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) rats and receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated RAW264.7 cells. Methods: The bone mineral density and 3D morphometric parameters of hind paws in AIA rats were measured using micro computed tomography (μCT) imaging. The activity of osteoclast cells was estimated based on tartrate-resistant acid phosphatase (TRAP) staining in specimens from the rats. In vitro TRAP activity was investigated using RANKL-stimulated RAW264.7 cells. The amount of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) protein was measured by western blot analysis. The expression of Nfatc1, its regulator genes, its upstream factors, and osteoclast-functional genes were investigated. Results: In addition to the suppression of bone resorption and lesions of bone trabeculae of AIA rats, IGU significantly decreased the number of TRAP-positive cells in the calcaneal bones. Moreover, this drug inhibited the differentiation of RANKL-stimulated RAW264.7 cells into osteoclasts, which were identified morphologically and functionally. IGU decreased the amount of NFATc1 protein and improved the altered expression of NFATc1-associated genes and osteoclast-functional genes. Conclusions: IGU suppressed osteoclastogenesis and bone resorption via the RANKL-NFATc1 pathway, suggesting such effect would be expected in clinical use.展开更多
BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complet...BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.展开更多
Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and b...Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and bone resorption.Treg cells that were isolated and purified from peripheral blood mononuclear cells(PBMCs)of healthy adults inhibited both the differentiation of osteoclasts(OCs)from human embryo bone marrow cells(BMCs)and the pit formation in a dose-dependent manner.In cell cocultures,the production levels of both interleukin-10(IL-10)and transforming growth factor-beta 1(TGF-β1)were proportionally upregulated as the ratio of Treg cells to BMCs was increased,and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies.Treatment of BMC and Treg cell cocultures with 17β-estradiol(E2)at concentrations between 10^(-7) and 10^(-9) mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone;this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression.These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1.E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells.Therefore,Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis(PMO).展开更多
Purpose The purpose of this study is to review the urine products of bone breakdown as markers of bone resorption and usefulness of urinary hydroxyproline.Data Related researches published in 1985 -2000 were systemati...Purpose The purpose of this study is to review the urine products of bone breakdown as markers of bone resorption and usefulness of urinary hydroxyproline.Data Related researches published in 1985 -2000 were systematically reviewed.Results Bone markers could be used for early diagnosis of bone metabolic diseases. Biochemical markers of bone resorption that reflect osteoclast activity and/or collagen degradation provide a new and potentially important clinical tool for the assessment and monitoring of bone metabolism. Assessment of bone resorption can be achieved with measurement of urinary hydroxylysine glycosides, urinary excretion of the collagen pyridinium cross-links, urinary excretion of type I collagen telopeptide breakdown products (cross-linked telopeptides) and urinary hydroxyproline.Conclusion Urinary hydroxyproline has been in use as a marker of bone resorption, but it lacks sensitivity and specificity. It is a modified aminoacid that is a metabolic product of collagen breakdown. Hydroxyproline may be released either free or with fragments of the collagen molecule attached during bone resorption, and it is also liberated by the breakdown of complement and nonskeletal collagen.展开更多
In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and...In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and the ways to prevent it should be explored.The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles.Macrophage colony stimulating factor(M-CSF)and receptor activator of NF-kB ligand(RANKL)were used to generate osteoclasts from RAW264.7 precursors.The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay.The cells were treated with titanium particles,titanium particles with icariine and culture medium only(control),respectively.At 48 h after treatment,the expression level of receptor activator of NF-kB(RANK)was detected by ELISA,and messenger RNA(mRNA)levels of tartrate-resistant acid phosphatase(TRAP),matrix metalloproteinase 9(MMP-9),carbonic anhydrase II(CAII)and Cathepsin K(CtsK)were determined by real-time polymerase chain reaction.Western blot was applied to analyze the expression levels of TRAP,RANK and CtsK.In addition,bone chips were cultured in the above conditions,and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips.After treatment with icariine,expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium,mRNA and protein levels of TRAP,CAII,MMP-9 and CtsK were reduced as well.In addition,the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging.Icariine could inhibit bone resorption of osteoclast induced by titanium particle,and it might be used as a promising drug for treating of aseptic loosening.展开更多
Radiographic changes consisting of al- terations in mineral content, osteopaenia or destructive neuropathy that occur following successful finger replantation have already been described. We report our experience abou...Radiographic changes consisting of al- terations in mineral content, osteopaenia or destructive neuropathy that occur following successful finger replantation have already been described. We report our experience about four fingers in three individuals in whom bone changes developed in the first three months postoperatively with complete ＂restitution ad integrum＂. Three patients, 21-49 years old （average 36 years） sustained a clean-cut amputation of four fingers. The first patient had an amputation at the base of the middle phalanx of the index finger and the second patient at the base of the proximal phalanx of the ring finger. The third had an amputation at the base of the first metacarpal bone and the proxi- mal phalanx of the small finger in a five finger amputation. In the first case, two dorsal veins and two palmar digital arteries and nerves were repaired. In the second case, one pal- mar artery and one dorsal vein were reanastomosed. In the third case at the thumb, two dorsal veins and two palmar digital arteries and nerves were reconstructed. At the small finger, one dorsal vein, one palmar digital artery and twodigital nerves were reconstructed. Bone fixation was achieved with two and three K-wires or tension-band wiring. Replantation was successful in all cases. Three weeks after replantation, the X-rays showed rapid development of osteopaenia in the juxtaarticular region and metaphyses of the bone. These changes were followed by subperiosteal, intracortical and endosteal bone resorption. No further surgical procedures or splintage were needed and hand therapy was not discontinued. At 10-13 weeks （average 12 weeks） postoperatively, the X-rays showed a complete recovery with new periosteal bone formation. We suggest that the radiographic changes after finger replantation are transient, first evident subperiosteally and progressing centrally. They may reflect small-vessel compromise and microinfarction and transient hyperemia secondary to neurovascular damage or to sympathetic progressive recovery.展开更多
The effect of La^(3+) on formation of osteoclast-like cells in rabbit bone marrow cells induced by 1,25-dihydroxyvitamin D_3 and their bone-resorbing activity was evaluated by counting the number of tartrate resistant...The effect of La^(3+) on formation of osteoclast-like cells in rabbit bone marrow cells induced by 1,25-dihydroxyvitamin D_3 and their bone-resorbing activity was evaluated by counting the number of tartrate resistant-acid phosphatase-positive [TRAP(+)] multi-nucleated cells and measuring the number and surface area of bone resorption pits with photomicrography and image analysis. The formation and morphological characteristics of osteoclast-like cells and bone resorption pits were observed under a phase contrast inverted microscope. La^(3+) promotes the formation of osteoclast-like cells at the concentration of 1.00×10^(-8)mol·L^(-1) compared with the control group(P<(0.01)), whereas no significant change in cell number is observed at higher concentrations(1.00×10^(-5), (1.00×)10^(-6) and 1.00×10^(-7) mol·L^(-1))(P>0.05). La^(3+) at the concentration of 1.00×10^(-8)mol·L^(-1) also increases the number and surface area of the resorption pits(P<0.01), but inhibits the bone-resorbing activity dose-dependently(P<0.01)at higher concentrations(1.00×10^(-5), 1.00×10^(-6) and 1.00×10^(-7) mol·L^(-1)). These findings suggest that La^(3+) may promote or inhibit the formation and bone-resorbing activity of osteoclast-like cells depending on its concentration.展开更多
The effects of lanthanum （Ⅲ） on the bone resorbing activity of rabbit mature osteoclasts （OCs） in the presence of osteoblasts （OBs） were studied in vitro by measuring the number and area of absorption pits. La...The effects of lanthanum （Ⅲ） on the bone resorbing activity of rabbit mature osteoclasts （OCs） in the presence of osteoblasts （OBs） were studied in vitro by measuring the number and area of absorption pits. La（ Ⅲ ） at concentrations ranging from 1.00 × 10^-5 to 1.00 × 10^-8 mol·L^-1 show no effect on mature OC number （P 〉 0.05）. In the OC-OB coculture systems without La（Ⅲ ）, osteoblasts alone did not influence the pit number and area whether the two kinds of cells were in contact or not （ P 〉 0.05）. Under the OC-OB not-in-contact condition, the effect of La（ Ⅲ ） on the bone-resorbing activity of OCs was similar to that of La（Ⅲ） in the absence of OBs （P 〉 0.05）. However, while OCs were in direct contact with OBs, the inhibitory effects of La（ Ⅲ ） on OCs＇ bone-resorbing activity decreased at the concentrations of 1.00 × 10^-5, 1.00×10^-6 and 1.00×10^-7mol·L^-1, and the promotion effects increased at 1.00×10^-8mol·L^-1 （P 〈0.05）. The results suggest that direct cell-cell contact between OC and OB be essential for OBs to play their role in regulating the response of OCs to La（ Ⅲ ）.展开更多
Apical periodontitis, dominated by dense inflammatory infiltrates and increased osteoclast activities, can lead to alveolar bone destruction and tooth loss. It is believed that miRNA participates in regulating various...Apical periodontitis, dominated by dense inflammatory infiltrates and increased osteoclast activities, can lead to alveolar bone destruction and tooth loss. It is believed that miRNA participates in regulating various biological processes, osteoclastogenesis included. This study aims to investigate the differential expression of miRNAs in rat apical periodontitis and explore their functional target genes. Microarray analysis was used to identify differentially expressed miRNAs in apical periodontitis. Bioinformatics technique was applied for predicting the target genes of differentially expressed miRNAs and their biological functions. The result provided us with an insight into the potential biological effects of the differentially expressed miRNAs and showed particular enrichment of target genes involved in the MAPK signaling pathways. These findings may highlight the intricate and specific roles of miRNA in inflammation and osteoclastogenesis, both of which are key aspects of apical periodontitis, thus contributing to the future investigation into the etiology, under- lying mechanism and treatment of apical periodontitis.展开更多
Matrix metalloproteinases (MMPs), a sort of irnportant enzymes involved in extracellular matrix metabolism, play critical r0Ies in the process of tissues remodeling, wound healing and metastasis of tumors. Dot blot an...Matrix metalloproteinases (MMPs), a sort of irnportant enzymes involved in extracellular matrix metabolism, play critical r0Ies in the process of tissues remodeling, wound healing and metastasis of tumors. Dot blot and in situ hybridization were used in this study to detect the expression and localization of MMP- 9, an important proteolytic enzyme implicated in bone resorption, in bone tissues. The results showed that the level of MMP-9 mRNA expression in osteoporotic bone tissues was significantly higher than that in normal control group and the cell types that expressed MMP-9 mRNA incIuded mono- and multi-nuclear osteoclasts and some lining cells on the surface of bone matrix. It was suggested that MMP-9 play a key role in the development of bone loss in osteoporosis.展开更多
OBJECTIVE:To determine the effect of an esculetin formulation(at 97.4%purity)on osteoporosis,and to investigate the potential underlying molecular mechanism(s).METHODS:Sixty specific pathogen free-grade female Wistar ...OBJECTIVE:To determine the effect of an esculetin formulation(at 97.4%purity)on osteoporosis,and to investigate the potential underlying molecular mechanism(s).METHODS:Sixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups:blank control(n=12),sham(n=12),and model(n=36).The model group were bilaterally ovariectomized.The sham group had the tissue surrounding the ovaries removed,while the ovaries were retained.After 3 months,the model group was randomly divided into three subgroups:OVX(n=12),positive control(n=12),and esculetin(n=12).The positive control group and the esculetin group were intragastrically administered diethylstilbestrol(0.046 mgkd^(-1)),respec·kg^(-1)tively,·d^(-1))or esculetin(384 mgg^(-1)once per day for 6 consecu··-tive days;medication administration was then stopped for 1 d,before being administered for another 6 consecutive days.All rats were treated for 3months.Samples were collected at the end of the treatment period.An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density,and histomorphometric analysis was performed to measure bone mass,bone formation,and bone resorption.Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6(IL-6),osteoprotegerin(OPG),and receptor activator of nuclear factor-kappa B ligand(RANKL).Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells.RESULTS:Compared with the OVX group,the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume,and significantly smaller trabecular resorption surface.The percentage of trabecular formation surface,average osteoid width,trabecular bone mineralization rate,and cortical bone mineralization rate did not significantly differ between groups.Compared with the sham group,the esculetin group had significantly decreased serum levels of IL-6and RANKL,and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells;however,there was no significant difference between groups in OPG.CONCLUSION:Esculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells,and decreasing serum IL-6 concentration.This indicates that the therapeutic effect of esculetin on osteoporosis occurs via decreased bone resorption.展开更多
BACKGROUND Severe horizontal bone deficiency of the maxillary anterior region is considered a major challenge in reconstruction and successful implant placement.Various approaches have been developed to augment bone v...BACKGROUND Severe horizontal bone deficiency of the maxillary anterior region is considered a major challenge in reconstruction and successful implant placement.Various approaches have been developed to augment bone volume.Of these approaches,onlay bone graft,alveolar bone splitting,and guided bone regeneration have been suggested.CASE SUMMARY A 22-year-old female patient,with no previous medical history,presented to the Department of Oral Implantology,Wuhan University due to a missing right maxillary incisor.The X-ray results showed severe horizontal bone deficiency,with an available bone width of 3.1-4.0 mm.The two bone blocks sandwich technique was performed to augment the bone volume.After 6 months healing,X-ray results showed that the newly formed alveolar ridge dimension increased to 4.7-9.5 mm horizontally.Implant insertion surgery was performed and allceramic restorations were fabricated.The implant was stable at the 1-year followup visit after restoration,and the X-ray showed a stable bone level around the dental implant.The scores for the pink esthetic score and white esthetic score were 12 and 8,respectively,and the patient was satisfied with the esthetic outcome.CONCLUSION The two bone blocks sandwich technique may be an alternative treatment option in augmenting severe horizontal bone deficiency of the anterior maxilla.展开更多
Regulator of G-protein Signaling 10(Rgsl0)plays an important function in osteoclast differentiation.However,the role of Rgsl0 in immune cells and inflammatory responses,which activate osteoclasts in inflam-matory lesi...Regulator of G-protein Signaling 10(Rgsl0)plays an important function in osteoclast differentiation.However,the role of Rgsl0 in immune cells and inflammatory responses,which activate osteoclasts in inflam-matory lesions,such as bacteria-induced periodontal disease lesions,remains largely unknown.In this study,we used an adeno-associated virus(AAV-)mediated RNAi(AAV-shRNA-Rgs10)knockdown approach to study Rgsl0's function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease.We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption,in vitro and in vivo.Interestingly,local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells,T-cells and osteoclasts,and protected the periodontal tissues from local inflammatory damage and bone destruction.Importantly,AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines.Our results demonstrate that AAV-shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously.Our data indicate that Rgsl0 may regulate dendritic cell proliferation and maturation,as well as the subsequent stimulation of T-cell proliferation and maturation,and osteoclast differentiation and acti-vation.Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.展开更多
AIM:To investigate the postprandial response of bone turnover markers in patients with Crohn’s disease(CD).METHODS:Fifty nine patients with CD aged 38±14years,and 45 healthy individuals matched for age and body ...AIM:To investigate the postprandial response of bone turnover markers in patients with Crohn’s disease(CD).METHODS:Fifty nine patients with CD aged 38±14years,and 45 healthy individuals matched for age and body mass index were included in the study.All participants underwent an oral glucose tolerance test(OGTT)after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type?Ⅰ?collagen(CTX-Ⅰ)and the bone formation marker procollagen type?Ⅰ?N propeptide were measured.Activity of the disease was assessed by calculation of the Crohn’s disease activity index(CDAI).RESULTS:Serum CTX-I was significantly higher in patients compared to controls(CTX-I:453±21 pg/mL vs 365±25 pg/mL,P=0.008),and values were significantly correlated with the activity of the disease(r=0.435,P=0.001).Results from OGTT-induced suppression of CTX-I showed two different trends.Patients with more active disease(assessed as CDAI>150)had a more excessive suppression of CTX-I compared to controls(55%vs 43%P<0.001),while patients on remission(assessed as CDAI<150)demonstrated an attenuated CTX-I suppression(30%vs 43%P<0.001).In line with this,CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease(r=0.913,P<0.001).CONCLUSION:The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.展开更多
Residual ridge resorption(RRR)is the decrease in the jaw structure that follows tooth extraction.It is a multifactorial disorder,but reports on the associated genetic factors are scarce,particularly amongst the Saudis...Residual ridge resorption(RRR)is the decrease in the jaw structure that follows tooth extraction.It is a multifactorial disorder,but reports on the associated genetic factors are scarce,particularly amongst the Saudis.This study aimed to investigate the role of single nucleotide polymorphisms(SNPs)in fibroblast growth factor receptor 1 oncogene partner 2(FGFR1OP2)in RRR development in Saudis.The study included 192 individuals(RRR=96;controls=96)attending outpatient clinics at the College of Dentistry,King Saud University.Demographic and clinical data were collected,the digital panoramic dental radiograph was obtained,and mandibular residual ridge height was measured.DNA was extracted from saliva and genotyping was conducted on“Sequenom MassARRAY iPLEX”.Genotype and allele frequencies of three SNPs were calculated and compared.The age at first diagnosis and bone height were compared in the three genotypes of each SNP.The age of the patients,age at first edentulism,and bone height ranged 21-80 years,12-70 years,and 13-34.6 mm,respectively.All three genotypes of the studied SNPs(rs2279351,rs78054962 and rs2306852)were identified.SNP rs2279351 associated significantly with RRR,and the mutant C allele was highly predisposing.No association was observed for the other two SNPs.The genotypes of all SNPs had an influence on age at first edentulism and bone height,but the results were not statistically different.Since FGFR1OP2 plays a role in the process of rapid wound healing in the oral cavity,it may be playing a role in the development of RRR by influencing the rate of resorption of the jawbone.SNP rs2279351 may alter its expression and hence RRR development.This study is limited due to small a sample size,and further large-scale studies are required to confirm this association and to consider rs2279351 as a possible marker of RRR development.展开更多
Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues.Dimethyl fumarate(DMF)has been used in the treatment of various immune-inflammat...Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues.Dimethyl fumarate(DMF)has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions.Here,we investigated for the first time the therapeutic effect of DMF on periodontitis.In vivo studies showed that DMF significantly inhibited periodontal destruction,enhanced mitophagy,and decreased the M1/M2 macrophage ratio.In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages,with improved mitochondrial function,inhibited oxidative stress,and increased mitophagy in RAW 264.7 cells.Furthermore,DMF increased intracellular mitochondrial Tu translation elongation factor(TUFM)levels to maintain mitochondrial homeostasis,promoted mitophagy,and modulated macrophage polarization,whereas TUFM knockdown decreased the protective effect of DMF.Finally,mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway.Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages,resulting in a shift in the balance of macrophage polarization,thereby attenuating periodontitis.Importantly,this study provides new insights into the prevention of periodontitis.展开更多
基金supported by NIH grants NIH/NIA R01AG069401(to L.Q.)NIH/NHLBI U54HL165442(to K.T.)P30AR069619(to Penn Center for Musculoskeletal Disorders).
文摘Bone resorption by osteoclasts is a critical step in bone remodeling,a process important for maintaining bone homeostasis and repairing injured bone.We previously identified a bone marrow mesenchymal subpopulation,marrow adipogenic lineage precursors(MALPs),and showed that its production of RANKL stimulates bone resorption in young mice using Adipoq-Cre.To exclude developmental defects and to investigate the role of MALPs-derived RANKL in adult bone,we generated inducible reporter mice(Adipoq-CreER Tomato)and RANKL deficient mice(Adipoq-CreER RANKLflox/flox,iCKO).Single cell-RNA sequencing data analysis and lineage tracing revealed that Adipoq+cells contain not only MALPs but also some mesenchymal progenitors capable of osteogenic differentiation.In situ hybridization showed that RANKL mRNA is only detected in MALPs,but not in osteogenic cells.RANKL deficiency in MALPs induced at 3 months of age rapidly increased trabecular bone mass in long bones as well as vertebrae due to diminished bone resorption but had no effect on the cortical bone.Ovariectomy(OVX)induced trabecular bone loss at both sites.RANKL depletion either before OVX or at 6 weeks post OVX protected and restored trabecular bone mass.Furthermore,bone healing after drill-hole injury was delayed in iCKO mice.Together,our findings demonstrate that MALPs play a dominant role in controlling trabecular bone resorption and that RANKL from MALPs is essential for trabecular bone turnover in adult bone homeostasis,postmenopausal bone loss,and injury repair.
基金supported by projects from the National Natural Science Foundation of China(81370977,81570796 and 81370018)by the Shanghai Science and Technology Committee(14411960900)
文摘Bone is an endocrine organ involved in modulating glucose homeostasis. The role of the bone formation marker osteocalcin （OCN） in predicting diabetes was reported, but with conflicting results. No study has explored the association between baseline bone resorption activity and incident diabetes or prediabetes during follow-up. Our objective was to examine the relationship between the baseline bone resorption marker crosslinked C-telopeptide of type I collagen （CTX） and glycemic dysregulation after 4 years. This longitudinal study was conducted in a university teaching hospital. A total of 195 normal glucose tolerant （NGT） women at baseline were invited for follow-up. The incidence of diabetes and prediabetes （collectively defined as dysglycemia） was recorded. A total of 128 individuals completed the 4-year study. The overall conversion rate from NGT to dysglycemia was 31.3%. The incidence of dysglycemia was lowest in the middle tertile [16.3% （95% confidence interval （CI）, 6.8%-30.70/0）] compared with the lower [31.0% （95% CI, 17.2%-46.1%）] and upper [46.5% （95% CI, 31.2%-62.6%）] tertiles of CTX, with a significant difference seen between the middle and upper tertiles （P = 0.002 5）. After adjusting for multiple confounding variables, the upper tertile of baseline CTX was associated with an increased risk of incident dysglycemia, with an odds ratio of 7.09 （95% CI, 1.73-28.99） when the middle tertile was the reference. Osteoclasts actively regulate glucose homeostasis in a biphasic model that moderately enhanced bone resorption marker CTX at baseline provides protective effects against the deterioration of glucose metabolism, whereas an overactive osteoclastic function contributes to an increased risk of subsequent dysglycemia.
基金Supported by the National Science and Technology Major Project of the Ministry of Science and Technology of China,No.2022YFA1105800the National Natural Science Foundation of China,No.81970940.
文摘BACKGROUND The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years,which also may lead to some complications such as alveolar bone resorption or tooth root resorption.Low-intensity pulsed ultrasound(LIPUS),a noninvasive physical therapy,has been shown to promote bone fracture healing.It is also reported that LIPUS could reduce the duration of orthodontic treatment;however,how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear.AIM To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement(OTM)model and explore the underlying mechanisms.METHODS A rat model of OTM was established,and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections.In vitro,human bone marrow mesenchymal stem cells(hBMSCs)were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction,Western blot,alkaline phosphatase(ALP)staining,and Alizarin red staining.The expression of Yes-associated protein(YAP1),the actin cytoskeleton,and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA(siRNA)application via immunofluorescence.RESULTS The force treatment inhibited the osteogenic differentiation potential of hBMSCs;moreover,the expression of osteogenesis markers,such as type 1 collagen(COL1),runt-related transcription factor 2,ALP,and osteocalcin(OCN),decreased.LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force.Mechanically,the expression of LaminA/C,F-actin,and YAP1 was downregulated after force treatment,which could be rescued by LIPUS.Moreover,the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment.Consistently,LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo.The decreased expression of COL1,OCN,and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS.CONCLUSION LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis,which may be a promising strategy to reduce the orthodontic treatment process.
基金National Natural Science Foundation Project(No.81260275)。
文摘Bone sialoprotein(BSP)is an important non-collagen extracellular matrix protein(EMC)that promotes bone formation and induces bone resorption.BSP is secreted by odontoblasts,it plays an important role in cementum,alveolar bone formation and mineralization,and periodontal function.Bone resorption is controlled by a complex molecular network,and BSP can promote osteoclast differentiation and bone resorption.It is also associated with the metastasis of a range of malignancies.Osteoclasts(OC)are thought to be the only cells involved in bone resorption and play an important role in bone formation and late developmental remodeling.Osteoporosis and periodontal disease are caused by excessive bone resorption.This article will summarize the osteoclasts differentiation,the biological function of bone resorption,and explore the progress of the prevention and treatment of the related bone resorption diseases such as osteoporosis and periodontal disease through the regulation of osteoclasts.
文摘Introduction: The aim of this study was to observe an inhibition of bone resorption and osteoclastogenesis by iguratimod (IGU, T-614), a disease-modifying anti-rheumatic drug, using adjuvant-induced arthritis (AIA) rats and receptor activator of nuclear factor kappa-B ligand (RANKL)-stimulated RAW264.7 cells. Methods: The bone mineral density and 3D morphometric parameters of hind paws in AIA rats were measured using micro computed tomography (μCT) imaging. The activity of osteoclast cells was estimated based on tartrate-resistant acid phosphatase (TRAP) staining in specimens from the rats. In vitro TRAP activity was investigated using RANKL-stimulated RAW264.7 cells. The amount of nuclear factor of activated T-cells, cytoplasmic, calcineurin-dependent 1 (NFATc1) protein was measured by western blot analysis. The expression of Nfatc1, its regulator genes, its upstream factors, and osteoclast-functional genes were investigated. Results: In addition to the suppression of bone resorption and lesions of bone trabeculae of AIA rats, IGU significantly decreased the number of TRAP-positive cells in the calcaneal bones. Moreover, this drug inhibited the differentiation of RANKL-stimulated RAW264.7 cells into osteoclasts, which were identified morphologically and functionally. IGU decreased the amount of NFATc1 protein and improved the altered expression of NFATc1-associated genes and osteoclast-functional genes. Conclusions: IGU suppressed osteoclastogenesis and bone resorption via the RANKL-NFATc1 pathway, suggesting such effect would be expected in clinical use.
基金Supported by Russian Science Foundation Grant,No.24-15-00185.
文摘BACKGROUND Tuberculous osteitis is a chronic,granulomatous bone infection that frequently results in impaired bone healing following surgery.Despite surgical intervention and prolonged anti-tuberculous therapy,complete bone regeneration often remains unachieved,contributing to subsequent orthopedic complications.AIM To investigate the efficacy and safety of pamidronate in promoting bone regeneration following surgical treatment of experimental animal tuberculous osteitis.METHODS A controlled randomized basic study of rabbit femoral tuberculosis induced by Mycobacterium tuberculosis strain H37Rv included surgical removal of infected tissue and implantation of osteoinductive bone grafts with the following animal allocation to one of three groups:(1)Bisphosphonates alone;(2)Bisphosphonates combined with anti-tuberculous therapy;and(3)Anti-tuberculous therapy alone.The control group consisted of animals that received no surgical or medical treatment.Clinical evaluations,biochemical markers,micro-computed tomography imaging,and histomorphometry analyses were conducted at 3 months and 6 months postoperatively.RESULTS Pamidronate treatment significantly reduced early implant resorption,increased osteoblastic activity,improved trabecular bone regeneration,and maintained graft integrity compared to the anti-tuberculous therapy-only group.Histologically,pamidronate led to enhanced vascular remodeling and increased bone matrix formation.Crucially,bisphosphonate therapy demonstrated safety,compatibility with anti-tuberculous medications,and did not exacerbate tuberculous inflammation.Furthermore,micro-computed tomography analysis revealed a significant increase in trabecular thickness and density in pamidronate-treated groups,underscoring the anabolic effects of bisphosphonates.Morphometric evaluation confirmed a marked reduction in osteoclast number and activity at graft interfaces.These combined radiological,histological,and biochemical data collectively demonstrate the efficacy of pamidronate as an adjunctive agent in enhancing bone repair outcomes following surgical intervention for tuberculous osteitis.CONCLUSION A single intravenous dose of pamidronate significantly enhances bone regeneration and prevents implant resorption following surgical treatment of tuberculous osteitis.The following prospective studies are needed.
基金This work was supported by the National Key Research Program of China(No.2006CB944007,to DJL)the National Natural Science Foundation of China(No.30801502,to LW)+1 种基金the Shanghai Leading Academic Discipline Project B117(to DJL)the Program for Outstanding Medical Academic Leaders(to DJL).
文摘Cross-talk has been shown to occur between the immune system and bone metabolism pathways.In the present study,we investigated the impact of CD4^(+)CD25^(+)Foxp3^(+) regulatory T(Treg)cells on osteoclastogenesis and bone resorption.Treg cells that were isolated and purified from peripheral blood mononuclear cells(PBMCs)of healthy adults inhibited both the differentiation of osteoclasts(OCs)from human embryo bone marrow cells(BMCs)and the pit formation in a dose-dependent manner.In cell cocultures,the production levels of both interleukin-10(IL-10)and transforming growth factor-beta 1(TGF-β1)were proportionally upregulated as the ratio of Treg cells to BMCs was increased,and the inhibition of OC differentiation and bone resorption by Treg cells was completely reversed by anti-IL-10 and anti-TGF-β1 antibodies.Treatment of BMC and Treg cell cocultures with 17β-estradiol(E2)at concentrations between 10^(-7) and 10^(-9) mol/l suppressed OC differentiation and bone resorption more efficiently than it did in cultures of BMCs alone;this enhanced suppression occurred via the stimulation of Treg cell IL-10 and TGF-b1 expression.These data suggest that Treg cells suppress OC differentiation and bone resorption by secreting IL-10 and TGF-β1.E2 enhances the suppressive effects of Treg cells on OC differentiation and bone resorption by stimulating IL-10 and TGF-β1 secretion from these cells.Therefore,Treg cell-derived IL-10 and TGF-b1 are likely involved in the regulation of E2 on bone metabolism and represent potential therapeutic targets for the treatment of postmenopausal osteoporosis(PMO).
文摘Purpose The purpose of this study is to review the urine products of bone breakdown as markers of bone resorption and usefulness of urinary hydroxyproline.Data Related researches published in 1985 -2000 were systematically reviewed.Results Bone markers could be used for early diagnosis of bone metabolic diseases. Biochemical markers of bone resorption that reflect osteoclast activity and/or collagen degradation provide a new and potentially important clinical tool for the assessment and monitoring of bone metabolism. Assessment of bone resorption can be achieved with measurement of urinary hydroxylysine glycosides, urinary excretion of the collagen pyridinium cross-links, urinary excretion of type I collagen telopeptide breakdown products (cross-linked telopeptides) and urinary hydroxyproline.Conclusion Urinary hydroxyproline has been in use as a marker of bone resorption, but it lacks sensitivity and specificity. It is a modified aminoacid that is a metabolic product of collagen breakdown. Hydroxyproline may be released either free or with fragments of the collagen molecule attached during bone resorption, and it is also liberated by the breakdown of complement and nonskeletal collagen.
基金This work was supported by grants from Natural Science Foundation of China(81302986)Young Foundation of Fujian Province Health Department,China(no.2007-2-37)Bureau of Science and Technology,Fuzhou(no.2009-G-104).
文摘In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and the ways to prevent it should be explored.The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles.Macrophage colony stimulating factor(M-CSF)and receptor activator of NF-kB ligand(RANKL)were used to generate osteoclasts from RAW264.7 precursors.The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay.The cells were treated with titanium particles,titanium particles with icariine and culture medium only(control),respectively.At 48 h after treatment,the expression level of receptor activator of NF-kB(RANK)was detected by ELISA,and messenger RNA(mRNA)levels of tartrate-resistant acid phosphatase(TRAP),matrix metalloproteinase 9(MMP-9),carbonic anhydrase II(CAII)and Cathepsin K(CtsK)were determined by real-time polymerase chain reaction.Western blot was applied to analyze the expression levels of TRAP,RANK and CtsK.In addition,bone chips were cultured in the above conditions,and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips.After treatment with icariine,expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium,mRNA and protein levels of TRAP,CAII,MMP-9 and CtsK were reduced as well.In addition,the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging.Icariine could inhibit bone resorption of osteoclast induced by titanium particle,and it might be used as a promising drug for treating of aseptic loosening.
文摘Radiographic changes consisting of al- terations in mineral content, osteopaenia or destructive neuropathy that occur following successful finger replantation have already been described. We report our experience about four fingers in three individuals in whom bone changes developed in the first three months postoperatively with complete ＂restitution ad integrum＂. Three patients, 21-49 years old （average 36 years） sustained a clean-cut amputation of four fingers. The first patient had an amputation at the base of the middle phalanx of the index finger and the second patient at the base of the proximal phalanx of the ring finger. The third had an amputation at the base of the first metacarpal bone and the proxi- mal phalanx of the small finger in a five finger amputation. In the first case, two dorsal veins and two palmar digital arteries and nerves were repaired. In the second case, one pal- mar artery and one dorsal vein were reanastomosed. In the third case at the thumb, two dorsal veins and two palmar digital arteries and nerves were reconstructed. At the small finger, one dorsal vein, one palmar digital artery and twodigital nerves were reconstructed. Bone fixation was achieved with two and three K-wires or tension-band wiring. Replantation was successful in all cases. Three weeks after replantation, the X-rays showed rapid development of osteopaenia in the juxtaarticular region and metaphyses of the bone. These changes were followed by subperiosteal, intracortical and endosteal bone resorption. No further surgical procedures or splintage were needed and hand therapy was not discontinued. At 10-13 weeks （average 12 weeks） postoperatively, the X-rays showed a complete recovery with new periosteal bone formation. We suggest that the radiographic changes after finger replantation are transient, first evident subperiosteally and progressing centrally. They may reflect small-vessel compromise and microinfarction and transient hyperemia secondary to neurovascular damage or to sympathetic progressive recovery.
文摘The effect of La^(3+) on formation of osteoclast-like cells in rabbit bone marrow cells induced by 1,25-dihydroxyvitamin D_3 and their bone-resorbing activity was evaluated by counting the number of tartrate resistant-acid phosphatase-positive [TRAP(+)] multi-nucleated cells and measuring the number and surface area of bone resorption pits with photomicrography and image analysis. The formation and morphological characteristics of osteoclast-like cells and bone resorption pits were observed under a phase contrast inverted microscope. La^(3+) promotes the formation of osteoclast-like cells at the concentration of 1.00×10^(-8)mol·L^(-1) compared with the control group(P<(0.01)), whereas no significant change in cell number is observed at higher concentrations(1.00×10^(-5), (1.00×)10^(-6) and 1.00×10^(-7) mol·L^(-1))(P>0.05). La^(3+) at the concentration of 1.00×10^(-8)mol·L^(-1) also increases the number and surface area of the resorption pits(P<0.01), but inhibits the bone-resorbing activity dose-dependently(P<0.01)at higher concentrations(1.00×10^(-5), 1.00×10^(-6) and 1.00×10^(-7) mol·L^(-1)). These findings suggest that La^(3+) may promote or inhibit the formation and bone-resorbing activity of osteoclast-like cells depending on its concentration.
基金Project supported bythe National Natural Science Foundation of China (20031010 ,20271005)
文摘The effects of lanthanum （Ⅲ） on the bone resorbing activity of rabbit mature osteoclasts （OCs） in the presence of osteoblasts （OBs） were studied in vitro by measuring the number and area of absorption pits. La（ Ⅲ ） at concentrations ranging from 1.00 × 10^-5 to 1.00 × 10^-8 mol·L^-1 show no effect on mature OC number （P 〉 0.05）. In the OC-OB coculture systems without La（Ⅲ ）, osteoblasts alone did not influence the pit number and area whether the two kinds of cells were in contact or not （ P 〉 0.05）. Under the OC-OB not-in-contact condition, the effect of La（ Ⅲ ） on the bone-resorbing activity of OCs was similar to that of La（Ⅲ） in the absence of OBs （P 〉 0.05）. However, while OCs were in direct contact with OBs, the inhibitory effects of La（ Ⅲ ） on OCs＇ bone-resorbing activity decreased at the concentrations of 1.00 × 10^-5, 1.00×10^-6 and 1.00×10^-7mol·L^-1, and the promotion effects increased at 1.00×10^-8mol·L^-1 （P 〈0.05）. The results suggest that direct cell-cell contact between OC and OB be essential for OBs to play their role in regulating the response of OCs to La（ Ⅲ ）.
基金supported by JCPT2011-9 and SKLODSCU 20130012 to XDZNSFC grant 81200760 and SKLODSCU 20130014 to LWZ
文摘Apical periodontitis, dominated by dense inflammatory infiltrates and increased osteoclast activities, can lead to alveolar bone destruction and tooth loss. It is believed that miRNA participates in regulating various biological processes, osteoclastogenesis included. This study aims to investigate the differential expression of miRNAs in rat apical periodontitis and explore their functional target genes. Microarray analysis was used to identify differentially expressed miRNAs in apical periodontitis. Bioinformatics technique was applied for predicting the target genes of differentially expressed miRNAs and their biological functions. The result provided us with an insight into the potential biological effects of the differentially expressed miRNAs and showed particular enrichment of target genes involved in the MAPK signaling pathways. These findings may highlight the intricate and specific roles of miRNA in inflammation and osteoclastogenesis, both of which are key aspects of apical periodontitis, thus contributing to the future investigation into the etiology, under- lying mechanism and treatment of apical periodontitis.
文摘Matrix metalloproteinases (MMPs), a sort of irnportant enzymes involved in extracellular matrix metabolism, play critical r0Ies in the process of tissues remodeling, wound healing and metastasis of tumors. Dot blot and in situ hybridization were used in this study to detect the expression and localization of MMP- 9, an important proteolytic enzyme implicated in bone resorption, in bone tissues. The results showed that the level of MMP-9 mRNA expression in osteoporotic bone tissues was significantly higher than that in normal control group and the cell types that expressed MMP-9 mRNA incIuded mono- and multi-nuclear osteoclasts and some lining cells on the surface of bone matrix. It was suggested that MMP-9 play a key role in the development of bone loss in osteoporosis.
基金Supported by Independent Subject Selection Project of the China Academy of Chinese Medical Sciences:Research on the New Function of Cortex Fraxini in the Treatment of Osteoporosis(No.YZ-1411)
文摘OBJECTIVE:To determine the effect of an esculetin formulation(at 97.4%purity)on osteoporosis,and to investigate the potential underlying molecular mechanism(s).METHODS:Sixty specific pathogen free-grade female Wistar rats were randomly assigned to three groups:blank control(n=12),sham(n=12),and model(n=36).The model group were bilaterally ovariectomized.The sham group had the tissue surrounding the ovaries removed,while the ovaries were retained.After 3 months,the model group was randomly divided into three subgroups:OVX(n=12),positive control(n=12),and esculetin(n=12).The positive control group and the esculetin group were intragastrically administered diethylstilbestrol(0.046 mgkd^(-1)),respec·kg^(-1)tively,·d^(-1))or esculetin(384 mgg^(-1)once per day for 6 consecu··-tive days;medication administration was then stopped for 1 d,before being administered for another 6 consecutive days.All rats were treated for 3months.Samples were collected at the end of the treatment period.An Osteocore3 Digital 2D bone densitometer was used to test the bone mineral density,and histomorphometric analysis was performed to measure bone mass,bone formation,and bone resorption.Enzyme-linked immunosorbent assay analysis was used to measure the serum concentrations of interleukin-6(IL-6),osteoprotegerin(OPG),and receptor activator of nuclear factor-kappa B ligand(RANKL).Immunohistochemistry and in situ hybridization were performed to detect the protein and mRNA expressions of OPG and RANKL in osteoblasts and bone marrow stromal cells.RESULTS:Compared with the OVX group,the esculetin group had significantly greater femoral bone mineral density and tibial trabecular bone volume,and significantly smaller trabecular resorption surface.The percentage of trabecular formation surface,average osteoid width,trabecular bone mineralization rate,and cortical bone mineralization rate did not significantly differ between groups.Compared with the sham group,the esculetin group had significantly decreased serum levels of IL-6and RANKL,and significant downregulation of RANKL protein and mRNA expression levels in osteoblasts and bone marrow stromal cells;however,there was no significant difference between groups in OPG.CONCLUSION:Esculetin can increase bone mass by upregulating RANKL expression in osteoblasts and bone marrow stromal cells,and decreasing serum IL-6 concentration.This indicates that the therapeutic effect of esculetin on osteoporosis occurs via decreased bone resorption.
文摘BACKGROUND Severe horizontal bone deficiency of the maxillary anterior region is considered a major challenge in reconstruction and successful implant placement.Various approaches have been developed to augment bone volume.Of these approaches,onlay bone graft,alveolar bone splitting,and guided bone regeneration have been suggested.CASE SUMMARY A 22-year-old female patient,with no previous medical history,presented to the Department of Oral Implantology,Wuhan University due to a missing right maxillary incisor.The X-ray results showed severe horizontal bone deficiency,with an available bone width of 3.1-4.0 mm.The two bone blocks sandwich technique was performed to augment the bone volume.After 6 months healing,X-ray results showed that the newly formed alveolar ridge dimension increased to 4.7-9.5 mm horizontally.Implant insertion surgery was performed and allceramic restorations were fabricated.The implant was stable at the 1-year followup visit after restoration,and the X-ray showed a stable bone level around the dental implant.The scores for the pink esthetic score and white esthetic score were 12 and 8,respectively,and the patient was satisfied with the esthetic outcome.CONCLUSION The two bone blocks sandwich technique may be an alternative treatment option in augmenting severe horizontal bone deficiency of the anterior maxilla.
基金supported by NIH grants RC1DE-020533(Y.P.L.)and AR-055307(Y.P.L.)
文摘Regulator of G-protein Signaling 10(Rgsl0)plays an important function in osteoclast differentiation.However,the role of Rgsl0 in immune cells and inflammatory responses,which activate osteoclasts in inflam-matory lesions,such as bacteria-induced periodontal disease lesions,remains largely unknown.In this study,we used an adeno-associated virus(AAV-)mediated RNAi(AAV-shRNA-Rgs10)knockdown approach to study Rgsl0's function in immune cells and osteoclasts in bacteria-induced inflammatory lesions in a mouse model of periodontal disease.We found that AAV-shRNA-Rgs10 mediated Rgs10 knockdown impaired osteoclastogenesis and osteoclast-mediated bone resorption,in vitro and in vivo.Interestingly,local injection of AAV-shRNA-Rgs10 into the periodontal tissues in the bacteria-induced inflammatory lesion greatly decreased the number of dendritic cells,T-cells and osteoclasts,and protected the periodontal tissues from local inflammatory damage and bone destruction.Importantly,AAV-mediated Rgs10 knockdown also reduced local expression of osteoclast markers and pro-inflammatory cytokines.Our results demonstrate that AAV-shRNA-Rgs10 knockdown in periodontal disease tissues can prevent bone resorption and inflammation simultaneously.Our data indicate that Rgsl0 may regulate dendritic cell proliferation and maturation,as well as the subsequent stimulation of T-cell proliferation and maturation,and osteoclast differentiation and acti-vation.Our study suggests that AAV-shRNA-Rgs10 can be useful as a therapeutic treatment of periodontal disease.
文摘AIM:To investigate the postprandial response of bone turnover markers in patients with Crohn’s disease(CD).METHODS:Fifty nine patients with CD aged 38±14years,and 45 healthy individuals matched for age and body mass index were included in the study.All participants underwent an oral glucose tolerance test(OGTT)after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type?Ⅰ?collagen(CTX-Ⅰ)and the bone formation marker procollagen type?Ⅰ?N propeptide were measured.Activity of the disease was assessed by calculation of the Crohn’s disease activity index(CDAI).RESULTS:Serum CTX-I was significantly higher in patients compared to controls(CTX-I:453±21 pg/mL vs 365±25 pg/mL,P=0.008),and values were significantly correlated with the activity of the disease(r=0.435,P=0.001).Results from OGTT-induced suppression of CTX-I showed two different trends.Patients with more active disease(assessed as CDAI>150)had a more excessive suppression of CTX-I compared to controls(55%vs 43%P<0.001),while patients on remission(assessed as CDAI<150)demonstrated an attenuated CTX-I suppression(30%vs 43%P<0.001).In line with this,CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease(r=0.913,P<0.001).CONCLUSION:The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.
文摘Residual ridge resorption(RRR)is the decrease in the jaw structure that follows tooth extraction.It is a multifactorial disorder,but reports on the associated genetic factors are scarce,particularly amongst the Saudis.This study aimed to investigate the role of single nucleotide polymorphisms(SNPs)in fibroblast growth factor receptor 1 oncogene partner 2(FGFR1OP2)in RRR development in Saudis.The study included 192 individuals(RRR=96;controls=96)attending outpatient clinics at the College of Dentistry,King Saud University.Demographic and clinical data were collected,the digital panoramic dental radiograph was obtained,and mandibular residual ridge height was measured.DNA was extracted from saliva and genotyping was conducted on“Sequenom MassARRAY iPLEX”.Genotype and allele frequencies of three SNPs were calculated and compared.The age at first diagnosis and bone height were compared in the three genotypes of each SNP.The age of the patients,age at first edentulism,and bone height ranged 21-80 years,12-70 years,and 13-34.6 mm,respectively.All three genotypes of the studied SNPs(rs2279351,rs78054962 and rs2306852)were identified.SNP rs2279351 associated significantly with RRR,and the mutant C allele was highly predisposing.No association was observed for the other two SNPs.The genotypes of all SNPs had an influence on age at first edentulism and bone height,but the results were not statistically different.Since FGFR1OP2 plays a role in the process of rapid wound healing in the oral cavity,it may be playing a role in the development of RRR by influencing the rate of resorption of the jawbone.SNP rs2279351 may alter its expression and hence RRR development.This study is limited due to small a sample size,and further large-scale studies are required to confirm this association and to consider rs2279351 as a possible marker of RRR development.
基金Natural Science Foundation of China(grant nos.82270991)Zhejiang Provincial Natural Science Foundation of China/Outstanding Youth Science Foundation(grant no.LR21H140002)+4 种基金Medical Health Science and Technology Major Project of Zhejiang Provincial Health Commission(grant no.WKJ-ZJ-2311)Wenzhou Science and Technology Bureau Public Welfare Social Development(Medical and Health)Science and Technology Project(grant no.ZY2021015)Opening Research Fund from Shanghai Key Laboratory of Stomatology,Shanghai Ninth People’s Hospital,College of Stomatology,Shanghai Jiao Tong University School of Medicine(grant no.2022SKLS-KFKT011)Guangxi Key Laboratory of the Rehabilitation and Reconstruction for Oral and Maxillofacial Research(grant no.GXKLRROM2106)State Key Laboratory of Oral Diseases Open Fund(grant no.SKLOD2024OF08).
文摘Periodontitis is a common oral disease characterized by progressive alveolar bone resorption and inflammation of the periodontal tissues.Dimethyl fumarate(DMF)has been used in the treatment of various immune-inflammatory diseases due to its excellent anti-inflammatory and antioxidant functions.Here,we investigated for the first time the therapeutic effect of DMF on periodontitis.In vivo studies showed that DMF significantly inhibited periodontal destruction,enhanced mitophagy,and decreased the M1/M2 macrophage ratio.In vitro studies showed that DMF inhibited macrophage polarization toward M1 macrophages and promoted polarization toward M2 macrophages,with improved mitochondrial function,inhibited oxidative stress,and increased mitophagy in RAW 264.7 cells.Furthermore,DMF increased intracellular mitochondrial Tu translation elongation factor(TUFM)levels to maintain mitochondrial homeostasis,promoted mitophagy,and modulated macrophage polarization,whereas TUFM knockdown decreased the protective effect of DMF.Finally,mechanistic studies showed that DMF increased intracellular TUFM levels by protecting TUFM from degradation via the ubiquitin-proteasomal degradation pathway.Our results demonstrate for the first time that DMF protects mitochondrial function and inhibits oxidative stress through TUFM-mediated mitophagy in macrophages,resulting in a shift in the balance of macrophage polarization,thereby attenuating periodontitis.Importantly,this study provides new insights into the prevention of periodontitis.
