Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture....Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.展开更多
Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In ...Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.展开更多
NiTi alloy has been widely used as orthopedic implant materials due to its unique shape memory properties and superelasticity.However,implantation failure often occurs because of the poor antibacterial ability,antioxi...NiTi alloy has been widely used as orthopedic implant materials due to its unique shape memory properties and superelasticity.However,implantation failure often occurs because of the poor antibacterial ability,antioxidation property and corrosion resistance of the NiTi alloy.In order to overcome the above problems,we constructed Zn/polydopamine(PDA)/Chitosan-Catechol(CS-C)composite coating on the surface of NiTi alloy in this paper.The surface morphology and wettability of the coating were characterized by scanning electron microscopy(SEM)and optical contact angle measuring instrument,respectively.The results showed that the Zn/CS-C coating was successfully prepared,and exhibited good hydrophilic property,especially the sample Zn/PDA/CS-C-24 h.In addition,the corrosion resistance,antioxidation property and biological properties of the coating were systematically analyzed.The results indicated that the Zn/PDA/CS-C composite coating exhibited good corrosion resistance and antibacterial property,antioxidant property and osteogenic activity,especially sample Zn/PDA/CS-C-24 h.The sample Zn/PDA/CS-C-24 h could effectively protect osteoblasts from reactive oxygen species(ROS)damage and promote cell proliferation and osteoblast differentiation.This study provides a feasible and effective strategy for the surface modification of orthopedic implant.展开更多
Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(P...Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.展开更多
BACKGROUND Fracture is one of the most pervasive injuries in the musculoskeletal system,and there is a complex interaction between macrophages and adipose tissue-derived stem cells(ADSCs)in fracture healing.However,tw...BACKGROUND Fracture is one of the most pervasive injuries in the musculoskeletal system,and there is a complex interaction between macrophages and adipose tissue-derived stem cells(ADSCs)in fracture healing.However,two-dimensional(2D)coculture of macrophages and ADSCs can not accurately mimic the in vivo cell microenvironment.AIM To establish both 2D and 3D osteogenic coculture models to investigate the interaction between macrophages and ADSCs.METHODS After obtaining ADSCs from surgery and inducing differentiation of the THP1 cell line,we established 2D and 3D osteogenic coculture models.To assess the level of osteogenic differentiation,we used alizarin red staining and measured the relative expression levels of osteogenic differentiation markers osteocalcin,Runt-related transcription factor 2,and alkaline phosphatase through polymerase chain reaction.Verification was conducted by analyzing the expression changes of N-cadherin and the activation of the Wnt/β-catenin signaling pathway using western blotting.RESULTS In this study,it was discovered that macrophages in 3D culture inhibited osteogenic differentiation of ADSCs,contrary to the effect in 2D culture.This observation confirmed the significance of intricate intercellular connections in the 3D culture environment.Additionally,the 3D culture group exhibited significantly higher N-cadherin expression and showed reducedβ-catenin and Wnt1 protein levels compared to the 2D culture group.CONCLUSION Macrophages promoted ADSC osteogenic differentiation in 2D culture conditions but inhibited it in 3D culture.The 3D culture environment might inhibit the Wnt/β-catenin signaling pathway by upregulating N-cadherin expression,ultimately hindering the osteogenic differentiation of ADSCs.By investigating the process of osteogenesis in ADSCs,this study provides novel ideas for exploring 3D osteogenesis in ADSCs,fracture repair,and other bone trauma repair.展开更多
Zinc(Zn)-based materials show broad application prospects for bone repair due to their biodegradability and good biocompatibility.In particular,Zn metal foam has unique interconnected pore structure that facilitates i...Zinc(Zn)-based materials show broad application prospects for bone repair due to their biodegradability and good biocompatibility.In particular,Zn metal foam has unique interconnected pore structure that facilitates inward growth of new bone tissue,making it ideal candidates for orthopedic implants.However,pure Zn metal foam shows poor mechanical property,high degradation rate,and unsatisfactory osteogenic activity.Herein,Zinc-manganese(Zn-Mn)alloy foams were electrodeposited in Zn and Mn-containing electrolytes to overcome the concerns.The results showed that Mn could be incorporated into the foams in the form of MnZn_(13).Zn-Mn alloy foams showed better mechanical property and osteogenic activity as well as moderate degradation rate when compared with pure Zn metal foam.In addition,these properties could also be regulated by preparation process.The peak stress and osteogenic activity increased with deposition current(0.3‒0.5 A)and electrolyte pH(3‒5),but decreased with electrolyte temperature(20‒40℃),while the degradation rate exhibited opposite tendency,which suggests high deposition current and electrolyte pH and low electrolyte temperature can fabricate Zn-Mn alloy foam with favorable mechanical property,moderate degradation rate,and osteogenic activity.These findings provide a valuable reference for the design and fabrication of novel Zn-based biodegradable materials.展开更多
Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate int...Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate into osteogenic cells.After transfection with relevant plasmids,cell proliferation,cell cycle progression,and apoptosis were assessed.Alizarin red staining was used to detect calcium nodules in the cells,alkaline phosphatase(ALP)staining was used to detect ALP activity in the cells,and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels.An OP rat model was established using ovariectomy and micro-computed tomography scanning.Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the pathological conditions of bone tissues,while immunohistochemistry was conducted to detect RUNX2 in bone tissues.Results AST promoted the osteogenic differentiation of BMSCs,reduced miR-181d-5p expression levels,and increased SOX11 expression levels.Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs.miR-181d-5p was found to target SOX11 in hBMSCs.AST improved OP in rats,and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats.Conclusion AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.展开更多
BACKGROUND Periodontitis is an inflammatory disease caused by the host’s immune response and various interactions between pathogens,which lead to the loss of connective tissue and bone.In recent years,mesenchymal ste...BACKGROUND Periodontitis is an inflammatory disease caused by the host’s immune response and various interactions between pathogens,which lead to the loss of connective tissue and bone.In recent years,mesenchymal stem cell(SC)transplantation technology has become a research hotspot,which can form periodontal ligament,cementum,and alveolar bone through proliferation and differentiation.AIM To elucidate the regulatory effects of WD repeat-containing protein 36(WDR36)on the senescence,migration,and osteogenic differentiation of periodontal ligament SCs(PDLSCs).METHODS The migration and chemotaxis of PDLSCs were detected by the scratch-wound migration test and transwell chemotaxis test.Alkaline phosphatase(ALP)activity,Alizarin red staining,calcium content,and real-time reverse transcription polymerase chain reaction(RT-qPCR)of key transcription factors were used to detect the osteogenic differentiation function of PDLSCs.Cell senescence was determined by senescence-associatedβ-galactosidase staining.RESULTS The 24-hour and 48-hour scratch-wound migration test and 48-hour transwell chemotaxis test showed that overexpression of WDR36 inhibited the migration/chemotaxis of PDLSCs.Simultaneously,WDR36 depletion promoted the migration/chemotaxis of PDLSCs.The results of ALP activity,Alizarin red staining,calcium content,and RTqPCR showed that overexpression of WDR36 inhibited the osteogenic differentiation of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.Senescence-associatedβ-galactosidase staining showed that 0.1μg/mL icariin(ICA)and overexpression of WDR36 inhibited the senescence of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.CONCLUSION WDR36 inhibits the migration and chemotaxis,osteogenic differentiation,and senescence of PDLSCs;0.1μg/mL ICA inhibits the senescence of PDLSCs.Therefore,WDR36 might serve as a target for periodontal tissue regeneration and the treatment of periodontitis.展开更多
BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical chal...BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical challenge.Enhancer of zeste homolog 2(EZH2),a histone H3 lysine 27 methyltransferase,regulates osteogenesis through epigenetic mechanisms,but its role in SCAPs remains unclear.We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B(KDM2B),offering a target for therapeutic intervention.AIM To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.METHODS SCAPs were isolated from healthy human third molars(n=6 donors).Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays.EZH2 overexpression/knockdown models were established using lentiviral vectors.Protein interactions were analyzed by co-immunoprecipitation,transcriptomic changes via microarray(Affymetrix platform),and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction.In vivo bone formation was evaluated in immunodeficient mice(n=8/group)transplanted with SCAPs-hydroxyapatite scaffolds.Data were analyzed using Student’s t-test and ANOVA.RESULTS EZH2 overexpression increased osteogenic markers and mineralized nodule formation.In vivo,EZH2-overexpressing SCAPs generated 10%more bone/dentin-like tissue.Co-immunoprecipitation confirmed EZH2-KDM2B interaction,and peptide-mediated disruption of this binding enhanced osteogenesis.Transcriptome analysis identified 1648 differentially expressed genes(971 upregulated;677 downregulated),with pathway enrichment in Wnt/β-catenin signaling.CONCLUSION EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B,and targeted disruption of this axis offers a translatable strategy for bone regeneration.展开更多
Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed th...Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.展开更多
BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,...BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.展开更多
Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroot...Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.展开更多
Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors ...Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated,the potential mechanisms of O-GlcNAcylation in bone metabolism,particularly,in the osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)remains unexplored.In this study,the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed,assuming that it could trigger more scholars to focus on research related to OGlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.展开更多
BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.AIM To invest...BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.AIM To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms.METHODS 20 growing mice were randomly divided into two groups:Con group(control group,n=10)and Ex group(treadmill exercise group,n=10).Hematoxylin-eosin staining,immunohistochemistry,and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur.Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19(lncRNA H19).RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation.RESULTS Compared with the Con group,the expression of bone morphogenetic protein 2 was also significantly increased.The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density,bone volume fraction,and the number of trabeculae,and decreased trabecular segregation in the femur of mice.Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation.In addition,knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers,which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence.CONCLUSION Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice,thus enhancing the peak bone mass of mice.The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.展开更多
Introduction: Solitary exostoses are the most common benign tumors of the fertile metaphyses of the long bones of children. Their radiological diagnosis of metaphyseal bone growth must be confirmed on pathological exa...Introduction: Solitary exostoses are the most common benign tumors of the fertile metaphyses of the long bones of children. Their radiological diagnosis of metaphyseal bone growth must be confirmed on pathological examination. These tumors can remain asymptomatic for a long time and reveal themselves during a particularly vascular complication. The objective of this study was to describe the epidemiological, diagnostic, therapeutic and evolutionary aspects of these tumors. Patient and Observation: We report the case of a 15-year-old adolescent girl, with no particular pathological history, received in the pediatric surgery department of the Donka National Hospital (HND) of the Conakry University Hospital for recurrent acute painful swelling of the lower third of the left thigh in an afebrile context accompanied by lameness and stopping school for a few days (2 - 3 days). The symptoms appear to have evolved over the past 3 years and after physical activities. It regresses with rest, analgesics and non-steroidal anti-inflammatory drugs. The notion of trauma and sickle cell disease was not reported in the patient's clinical history. It is the persistence of the symptomatology which motivates the said consultation. On palpation, a small hard mass is noted at the expense of the internal metaphysis of the left distal femur. Deep palpation of this area causes a tingling sensation and during rapid mobilization of the knee. The remainder of the orthopedic examination was unremarkable. Standard x-ray of the femur shows a bony growth with a pointed tip from the distal metaphysis of the left femur. On surgical exploration, we noted a wedge-shaped exostosis oriented towards the vastus medialis muscle. Histological examination of the surgical specimen confirms osteogenic exostosis. There is no recurrence after 2 years. Conclusion: The distal femoral metaphysis is the most common location of solitary osteochondromas in children. Their definitive diagnosis requires the histology of the surgical specimen. Only symptomatic exostoses should be operated on in children.展开更多
For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ...For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ostogenesis and clearly reveal the influence factor.To this end,the fluorescent gold nanodots(Au NDs) with highly negative charges as osteogenic induction reagent are successfully synthesized,which display better than commercial osteogenic induction medium through the investigations of ALP activity(2.5 folds) and cytoskeleton staining(1.5 folds).Two kinds of oligopeptides with different bio-structures(cysteine,Cys and glutathione,GSH) are selected for providing surficial charges on Au NDs.It is revealed that Au-Cys with more negative charges(-51 mV) play better role than Au-GSH(-19 mV) in osteogenic differentiation,when both of them have same size(~2 nm),sphere shape and show similar cell uptake amount.To explore deeply,osteogenesis related signaling pathways are monitored,revealing that the enhancement of osteogenic differentiation was through autophagy signaling pathway triggered by Au-Cys.And the promotion of highly negative charges in osteogenic diffe rentiation was further proved via sliver nanodots(Ag NDs,Ag-Cys and Ag-GSH) and carbon nanodots(CDs,Cys-CDs and GSH-CDs).This work indicates part of insights during hBMSCs differentiation and provides a novel strategy in osteogenic differentiation process.展开更多
Objective:Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques.The aim of this study is to ...Objective:Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques.The aim of this study is to investigate the effect of connective tissue growth factor(CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells(MSCs).Methods:A CTGF-expressing plasmid(pCTGF) was constructed and transfected into MSCs.Then expressions of bone morphogenesis-related genes,proliferation rate,alkaline phosphatase activity,and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs.Results:Overexpression of CTGF was confirmed in pCTGF-MSCs.pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs(P<0.05).CTGF induced a 7.5-fold increase in cell migration over control(P<0.05).pCTGF transfection enhanced the expression of bone matrix proteins,such as bone sialo-protein,osteocalcin,and collagen type I in MSCs.The levels of alkaline phosphatase(ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0-and 3.0-fold higher than those of MSCs cultured in OS-medium,significantly higher than those of mock-MSCs and normal control MSCs(P<0.05).Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules.Conclusion:Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs,and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.展开更多
Periodontal diseases are infectious diseases that are characterized by progressive damage to dental support tissue.The major goal of periodontal therapy is to regenerate the periodontium destroyed by periodontal disea...Periodontal diseases are infectious diseases that are characterized by progressive damage to dental support tissue.The major goal of periodontal therapy is to regenerate the periodontium destroyed by periodontal diseases.Human periodontal ligament(PDL)tissue possesses periodontal regenerative properties,and periodontal ligament stem cells(PDLSCs)with the capacity for osteogenic differentiation show strong potential in clinical application for periodontium repair and regeneration.Noncoding RNAs(ncRNAs),which include a substantial portion of poly-A tail mature RNAs,are considered“transcriptional noise.”Recent studies show that ncRNAs play a major role in PDLSC differentiation;therefore,exploring how ncRNAs participate in the osteogenic differentiation of PDLSCs may help to elucidate the underlying mechanism of the osteogenic differentiation of PDLSCs and further shed light on the potential of stem cell transplantation for periodontium regeneration.In this review paper,we discuss the history of PDLSC research and highlight the regulatory mechanism of ncRNAs in the osteogenic differentiation of PDLSCs.展开更多
BACKGROUND In the clinical scenario,adult patients with periodontal diseases and dental malformation,characterized by dental crowding in lower anterior teeth with the thin biotype,often require orthodontic treatment.T...BACKGROUND In the clinical scenario,adult patients with periodontal diseases and dental malformation,characterized by dental crowding in lower anterior teeth with the thin biotype,often require orthodontic treatment.This case report aimed to evaluate the clinical and radiographic outcomes of periodontally accelerated osteogenic orthodontics(PAOO)combined with autologous platelet-rich fibrin(PRF)in an adult patient with class I malocclusion along with dental crowding,a thin periodontal biotype,and buccal plate deficiency.CASE SUMMARY A 32-year-old female complaining of dental crowding and gingival bleeding was referred to the orthodontic clinic.The patient underwent periodontal risk assessment prior to orthodontic treatment.She was diagnosed with a high risk of gingival recession due to dental crowding,root prominence,loss of buccal plates,and a thin gingival tissue biotype.The treatment regimen included PAOO combined with autologous PRF for alveolar augmentation and interproximal enamel reduction for moderate dental crowding.Clinically,PAOO-assisted orthodontic tooth movement in this case showed enhanced periodontium remodeling.Radiographic outcomes also showed statistically significant improvements(P<0.01)in the mandibular buccal alveolar bone.CONCLUSION This case report suggests the combination of autologous PRF with PAOO to enhance bone augmentation and long-term tissue support in adult orthodontic patients with periodontal disease.展开更多
The rapid degradation of magnesium(Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. I...The rapid degradation of magnesium(Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. In the present study, three Mg alloys, including Mg-0.8Ca(denoted as ZQ), Mg-0.8Ca-5Zn-1.5Ag(denoted as ZQ71) and Mg-0.8Ca-5Zn-2.5Ag(denoted as ZQ63), were fabricated by alloying with calcium(Ca), zinc(Zn) and silver(Ag). The results obtained from electrochemical corrosion tests and in vitro degradation evaluation demonstrated that the three Mg alloys exhibited distinct corrosion resistance, and ZQ71 exhibited the lowest degradation rate in vitro among them. After addition of Zn and Ag, the antibacterial potential of Mg alloys was also enhanced. The in vitro cell experiments showed that all the three Mg alloys had good biocompatibility. After implantation in a rat femoral defect, ZQ71 showed significantly higher osteogenic activity and bone substitution rate than ZQ63 and ZQ, due to its higher corrosion resistance as well as the stimulatory effects of the released metallic ions. In addition, the average daily degradation rate of each Mg alloy in vivo was significantly higher than that in vitro, as could be due to the implantation site located in the highly vascularized trabecular region. Importantly, the correlations between the in vitro and in vivo degradation parameters of the Mg alloys were systematically analyzed to find out the potential predictors of the in vivo degradation performance of the materials. The current work not only evaluated the clinical potential of the three biodegradable Mg alloys as bone grafts but also provided a feasible approach for predicting the in vivo degradation behavior of biodegradable materials.展开更多
基金supported by the National Key Research and Development Project (2021YFA1201404)National Natural Science Foundation of China Major Project (81991514)+6 种基金General Project (82272530, 82372459)Jiangsu Province Medical Innovation Center of Orthopedic Surgery (CXZX202214)Jiangsu Provincial Key Medical Center FoundationJiangsu Provincial Medical Outstanding Talent FoundationJiangsu Provincial Medical Youth Talent FoundationJiangsu Provincial Key Medical Talent Foundationthe Fundamental Research Funds for the Central Universities (14380493, 14380494)
文摘Osteoporosis represents a prevalent and debilitating comorbidity in patients diagnosed with type 2 diabetes mellitus(T2DM),which is characterized by suppressed osteoblast function and disrupted bone microarchitecture.In this study,we utilized male C57BL/6 J mice to investigate the role of SIRT3 in T2DM.Decreased SIRT3 expression and impaired mitochondrial quality control mechanism are observed in both in vitro and in vivo models of T2DM.Mechanistically,SIRT3 suppression results in hyperacetylation of FOXO3,hindering the activation of the PINK1/PRKN mediated mitophagy pathway and resulting in accumulation of dysfunctional mitochondria.Genetical overexpression or pharmacological activation of SIRT3 restores deacetylation status of FOXO3,thus facilitating mitophagy and ameliorating osteogenic impairment in T2DM.Collectively,our findings highlight the fundamental regulatory function of SIRT3 in mitochondrial quality control,crucial for maintaining bone homeostasis in T2DM.These insights not only enhance our understanding of the molecular mechanisms underlying diabetic osteoporosis but also identify SIRT3 as a promising therapeutic target for diabetic osteoporosis.
基金supported by National Natural Science Foundation of China(Nos.82322015,82171006)Sichuan Province Youth Science and Technology Innovation Team(No.2022JDTD0021)+3 种基金Sichuan Science and Technology Program(No.2022NSFSC0002)West China Hospital of Stomatology Sichuan University(No.RCDWJS2024-3)Sichuan Science and Technology Program(Nos.2023NSFSC1706,2024NSFSC1589)Postdoctoral Science Foundation of China(No.BX20220220)。
文摘Osteogenic ability impairment and myelosuppression are common complications of chemotherapy and many chemotherapeutics can affect the skeletal system.Skeletal system protection is necessary for cancer chemotherapy.In this study,osteogenic growth peptide(OGP)and tetrahedral framework nucleic-acid nanostructures(tFNAs)are combined to form a peptide-DNA complex OGP-tFNAs,which aims to combine the positive biological effect on tissue protection and regeneration.The bone marrow protection and bone formation effect of OGP-tFNAs are investigated in chemotherapy-induced myelosuppressive mice.The results show that OGP-tFNAs could reduce the cell damage degree from 5-fluorouracil(5-FU)in vitro and maintained the osteogenic differentiation potential.Furthermore,OGP-tFNAs accelerate bone defect regeneration in myelosuppressive mice.In conclusion,OGP-tFNAs could protect the osteogenic differentiation potential of bone marrow stromal cells(BMSCs)from 5-FU injury and maintain the bone formation ability of myelosuppressive mice suffering from chemotherapy.
基金jointly supported by the Natural Science Foundation of Shanxi Province(Nos.202203021222127,202403021212109).
文摘NiTi alloy has been widely used as orthopedic implant materials due to its unique shape memory properties and superelasticity.However,implantation failure often occurs because of the poor antibacterial ability,antioxidation property and corrosion resistance of the NiTi alloy.In order to overcome the above problems,we constructed Zn/polydopamine(PDA)/Chitosan-Catechol(CS-C)composite coating on the surface of NiTi alloy in this paper.The surface morphology and wettability of the coating were characterized by scanning electron microscopy(SEM)and optical contact angle measuring instrument,respectively.The results showed that the Zn/CS-C coating was successfully prepared,and exhibited good hydrophilic property,especially the sample Zn/PDA/CS-C-24 h.In addition,the corrosion resistance,antioxidation property and biological properties of the coating were systematically analyzed.The results indicated that the Zn/PDA/CS-C composite coating exhibited good corrosion resistance and antibacterial property,antioxidant property and osteogenic activity,especially sample Zn/PDA/CS-C-24 h.The sample Zn/PDA/CS-C-24 h could effectively protect osteoblasts from reactive oxygen species(ROS)damage and promote cell proliferation and osteoblast differentiation.This study provides a feasible and effective strategy for the surface modification of orthopedic implant.
文摘Osteogenesis is driven by the differentiation of osteoblasts and the mineralization of the bone matrix,with oral-derived stem cells playing a significant role in this process.Various post-translational modifications(PTMs),such as phosphorylation,acetylation,methylation,and glycosylation,regulate osteogenic differentiation(OD).These modifications influence the expression of osteogenic genes by modulating the activity of key transcription factors like runt-related transcription factor 2 and osterix.While the molecular mechanisms behind OD are increasingly understood,many questions remain,particularly regarding how PTMs control the specificity and efficiency of stem cell differentiation.Recent research into these modifications has underscored the potential of stem cell therapy for bone regeneration and treating bone-related diseases.This review summarizes the role of PTMs in the OD of oral-derived stem cells,discusses their clinical applications,and suggests future research directions.
文摘BACKGROUND Fracture is one of the most pervasive injuries in the musculoskeletal system,and there is a complex interaction between macrophages and adipose tissue-derived stem cells(ADSCs)in fracture healing.However,two-dimensional(2D)coculture of macrophages and ADSCs can not accurately mimic the in vivo cell microenvironment.AIM To establish both 2D and 3D osteogenic coculture models to investigate the interaction between macrophages and ADSCs.METHODS After obtaining ADSCs from surgery and inducing differentiation of the THP1 cell line,we established 2D and 3D osteogenic coculture models.To assess the level of osteogenic differentiation,we used alizarin red staining and measured the relative expression levels of osteogenic differentiation markers osteocalcin,Runt-related transcription factor 2,and alkaline phosphatase through polymerase chain reaction.Verification was conducted by analyzing the expression changes of N-cadherin and the activation of the Wnt/β-catenin signaling pathway using western blotting.RESULTS In this study,it was discovered that macrophages in 3D culture inhibited osteogenic differentiation of ADSCs,contrary to the effect in 2D culture.This observation confirmed the significance of intricate intercellular connections in the 3D culture environment.Additionally,the 3D culture group exhibited significantly higher N-cadherin expression and showed reducedβ-catenin and Wnt1 protein levels compared to the 2D culture group.CONCLUSION Macrophages promoted ADSC osteogenic differentiation in 2D culture conditions but inhibited it in 3D culture.The 3D culture environment might inhibit the Wnt/β-catenin signaling pathway by upregulating N-cadherin expression,ultimately hindering the osteogenic differentiation of ADSCs.By investigating the process of osteogenesis in ADSCs,this study provides novel ideas for exploring 3D osteogenesis in ADSCs,fracture repair,and other bone trauma repair.
基金supported by the Key Research and Development Program of Shanxi Province(202102130501007)the Natural Science Foundation of Shanxi Province(202403021212109,202203021211173)the Scientific and Technological Innovation Programs of Higher Education Institutions in Shanxi(2024L039).
文摘Zinc(Zn)-based materials show broad application prospects for bone repair due to their biodegradability and good biocompatibility.In particular,Zn metal foam has unique interconnected pore structure that facilitates inward growth of new bone tissue,making it ideal candidates for orthopedic implants.However,pure Zn metal foam shows poor mechanical property,high degradation rate,and unsatisfactory osteogenic activity.Herein,Zinc-manganese(Zn-Mn)alloy foams were electrodeposited in Zn and Mn-containing electrolytes to overcome the concerns.The results showed that Mn could be incorporated into the foams in the form of MnZn_(13).Zn-Mn alloy foams showed better mechanical property and osteogenic activity as well as moderate degradation rate when compared with pure Zn metal foam.In addition,these properties could also be regulated by preparation process.The peak stress and osteogenic activity increased with deposition current(0.3‒0.5 A)and electrolyte pH(3‒5),but decreased with electrolyte temperature(20‒40℃),while the degradation rate exhibited opposite tendency,which suggests high deposition current and electrolyte pH and low electrolyte temperature can fabricate Zn-Mn alloy foam with favorable mechanical property,moderate degradation rate,and osteogenic activity.These findings provide a valuable reference for the design and fabrication of novel Zn-based biodegradable materials.
基金supported by the National Natural Science Foundation of China(No.81700888).
文摘Objective This study aimed to investigate the effect of Astragalus(AST)on osteoporosis(OP)and the downstream mechanisms.Methods Human bone marrow-derived mesenchymal stem cells(hBMSCs)were induced to differentiate into osteogenic cells.After transfection with relevant plasmids,cell proliferation,cell cycle progression,and apoptosis were assessed.Alizarin red staining was used to detect calcium nodules in the cells,alkaline phosphatase(ALP)staining was used to detect ALP activity in the cells,and quantitative reverse transcription-polymerase chain reaction and western blotting were used to determine RUNX2 and Osterix expression levels.An OP rat model was established using ovariectomy and micro-computed tomography scanning.Hematoxylin and eosin staining and Masson’s trichrome staining were used to evaluate the pathological conditions of bone tissues,while immunohistochemistry was conducted to detect RUNX2 in bone tissues.Results AST promoted the osteogenic differentiation of BMSCs,reduced miR-181d-5p expression levels,and increased SOX11 expression levels.Restoring miR-181d-5p expression or reducing SOX11 expression levels reversed the effects of AST on the osteogenic differentiation of hBMSCs.miR-181d-5p was found to target SOX11 in hBMSCs.AST improved OP in rats,and miR-181d-5p overexpression or SOX11 inhibition reversed the therapeutic effects of AST on OP in rats.Conclusion AST promoted the osteogenic differentiation of hBMSCs and alleviated OP by targeting SOX11 via miR-181d-5p.
文摘BACKGROUND Periodontitis is an inflammatory disease caused by the host’s immune response and various interactions between pathogens,which lead to the loss of connective tissue and bone.In recent years,mesenchymal stem cell(SC)transplantation technology has become a research hotspot,which can form periodontal ligament,cementum,and alveolar bone through proliferation and differentiation.AIM To elucidate the regulatory effects of WD repeat-containing protein 36(WDR36)on the senescence,migration,and osteogenic differentiation of periodontal ligament SCs(PDLSCs).METHODS The migration and chemotaxis of PDLSCs were detected by the scratch-wound migration test and transwell chemotaxis test.Alkaline phosphatase(ALP)activity,Alizarin red staining,calcium content,and real-time reverse transcription polymerase chain reaction(RT-qPCR)of key transcription factors were used to detect the osteogenic differentiation function of PDLSCs.Cell senescence was determined by senescence-associatedβ-galactosidase staining.RESULTS The 24-hour and 48-hour scratch-wound migration test and 48-hour transwell chemotaxis test showed that overexpression of WDR36 inhibited the migration/chemotaxis of PDLSCs.Simultaneously,WDR36 depletion promoted the migration/chemotaxis of PDLSCs.The results of ALP activity,Alizarin red staining,calcium content,and RTqPCR showed that overexpression of WDR36 inhibited the osteogenic differentiation of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.Senescence-associatedβ-galactosidase staining showed that 0.1μg/mL icariin(ICA)and overexpression of WDR36 inhibited the senescence of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.CONCLUSION WDR36 inhibits the migration and chemotaxis,osteogenic differentiation,and senescence of PDLSCs;0.1μg/mL ICA inhibits the senescence of PDLSCs.Therefore,WDR36 might serve as a target for periodontal tissue regeneration and the treatment of periodontitis.
基金Supported by National Key Research and Development Program,No.2022YFA1104401Beijing Natural Science Foundation,No.7222075+1 种基金CAMS Innovation Fund for Medical Sciences,No.2019RU020Innovation Research Team Project of Beijing Stomatological Hospital,No.CXTD202204.
文摘BACKGROUND Stem cells from apical papilla(SCAPs)represent promising candidates for bone regenerative therapies due to their osteogenic potential.However,enhancing their differentiation capacity remains a critical challenge.Enhancer of zeste homolog 2(EZH2),a histone H3 lysine 27 methyltransferase,regulates osteogenesis through epigenetic mechanisms,but its role in SCAPs remains unclear.We hypothesized that EZH2 modulates SCAP osteogenic differentiation via interaction with lysine demethylase 2B(KDM2B),offering a target for therapeutic intervention.AIM To investigate the functional role and molecular mechanism of EZH2 in SCAP osteogenic differentiation.METHODS SCAPs were isolated from healthy human third molars(n=6 donors).Osteogenic differentiation was assessed via Alizarin red staining and alkaline phosphatase assays.EZH2 overexpression/knockdown models were established using lentiviral vectors.Protein interactions were analyzed by co-immunoprecipitation,transcriptomic changes via microarray(Affymetrix platform),and chromatin binding by chromatin immunoprecipitation-quantitative polymerase chain reaction.In vivo bone formation was evaluated in immunodeficient mice(n=8/group)transplanted with SCAPs-hydroxyapatite scaffolds.Data were analyzed using Student’s t-test and ANOVA.RESULTS EZH2 overexpression increased osteogenic markers and mineralized nodule formation.In vivo,EZH2-overexpressing SCAPs generated 10%more bone/dentin-like tissue.Co-immunoprecipitation confirmed EZH2-KDM2B interaction,and peptide-mediated disruption of this binding enhanced osteogenesis.Transcriptome analysis identified 1648 differentially expressed genes(971 upregulated;677 downregulated),with pathway enrichment in Wnt/β-catenin signaling.CONCLUSION EZH2 promotes SCAP osteogenesis via antagonistic interaction with KDM2B,and targeted disruption of this axis offers a translatable strategy for bone regeneration.
基金Indian Council of Medical Research,2020-0282/SCR/ADHOC-BMSDepartment of Science and Technology,India,DST/INSPIRE Fellowship:2021/IF210073.
文摘Mesenchymal stem cells(MSCs)originate from many sources,including the bone marrow and adipose tissue,and differentiate into various cell types,such as osteoblasts and adipocytes.Recent studies on MSCs have revealed that many transcription factors and signaling pathways control osteogenic development.Osteogenesis is the process by which new bones are formed;it also aids in bone remodeling.Wnt/β-catenin and bone morphogenetic protein(BMP)signaling pathways are involved in many cellular processes and considered to be essential for life.Wnt/β-catenin and BMPs are important for bone formation in mammalian development and various regulatory activities in the body.Recent studies have indicated that these two signaling pathways contribute to osteogenic differen-tiation.Active Wnt signaling pathway promotes osteogenesis by activating the downstream targets of the BMP signaling pathway.Here,we briefly review the molecular processes underlying the crosstalk between these two pathways and explain their participation in osteogenic differentiation,emphasizing the canonical pathways.This review also discusses the crosstalk mechanisms of Wnt/BMP signaling with Notch-and extracellular-regulated kinases in osteogenic differentiation and bone development.
基金Supported by São Paulo Research Foundation(FAPESP),No.2010/08918-9 and 2020/11564-6the KBSP Young Investigator Fellowship,No.2011/00204-0+2 种基金the DBF Fellowship,No.2019/27492-7the LMG Fellowship,No.2014/01395-1the CFB Fellowship,No.2014/14278-3.
文摘BACKGROUND Validation of the reference gene(RG)stability during experimental analyses is essential for correct quantitative real-time polymerase chain reaction(RT-qPCR)data normalisation.Commonly,in an unreliable way,several studies use genes involved in essential cellular functions[glyceraldehyde-3-phosphate dehydro-genase(GAPDH),18S rRNA,andβ-actin]without paying attention to whether they are suitable for such experimental conditions or the reason for choosing such genes.Furthermore,such studies use only one gene when Minimum Information for Publication of Quantitative Real-Time PCR Experiments guidelines recom-mend two or more genes.It impacts the credibility of these studies and causes dis-tortions in the gene expression findings.For tissue engineering,the accuracy of gene expression drives the best experimental or therapeutical approaches.We cultivated DPSCs under two conditions:Undifferentiated and osteogenic dif-ferentiation,both for 35 d.We evaluated the gene expression of 10 candidates for RGs[ribosomal protein,large,P0(RPLP0),TATA-binding protein(TBP),GAPDH,actin beta(ACTB),tubulin(TUB),aminolevulinic acid synthase 1(ALAS1),tyro-sine 3-monooxygenase/tryptophan 5-monooxygenase activation protein,zeta(YWHAZ),eukaryotic translational elongation factor 1 alpha(EF1a),succinate dehydrogenase complex,subunit A,flavoprotein(SDHA),and beta-2-micro-globulin(B2M)]every 7 d(1,7,14,21,28,and 35 d)by RT-qPCR.The data were analysed by the four main algorithms,ΔCt method,geNorm,NormFinder,and BestKeeper and ranked by the RefFinder method.We subdivided the samples into eight subgroups.RESULTS All of the data sets from clonogenic and osteogenic samples were analysed using the RefFinder algorithm.The final ranking showed RPLP0/TBP as the two most stable RGs and TUB/B2M as the two least stable RGs.Either theΔCt method or NormFinder analysis showed TBP/RPLP0 as the two most stable genes.However,geNorm analysis showed RPLP0/EF1αin the first place.These algorithms’two least stable RGs were B2M/GAPDH.For BestKeeper,ALAS1 was ranked as the most stable RG,and SDHA as the least stable RG.The pair RPLP0/TBP was detected in most subgroups as the most stable RGs,following the RefFinfer ranking.CONCLUSION For the first time,we show that RPLP0/TBP are the most stable RGs,whereas TUB/B2M are unstable RGs for long-term osteogenic differentiation of human DPSCs in traditional monolayers.
基金supported by the National Natural Science Foundation of China(82202352,82271629)the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University(ZNLH202202)+1 种基金the China Postdoctoral Science Foundation Funded Project(2023M732711)the Wenzhou Medical University grant(QTJ23004)。
文摘Background:Most bone-related injuries to grassroots troops are caused by training or accidental injuries.To establish preventive measures to reduce all kinds of trauma and improve the combat effectiveness of grassroots troops,it is imperative to develop new strategies and scafolds to promote bone regeneration.Methods:In this study,a porous piezoelectric hydrogel bone scafold was fabricated by incorporating polydopamine(PDA)-modified ceramic hydroxyapatite(PDA-hydroxyapatite,PHA)and PDA-modified barium titanate(PDABaTiO_(3),PBT)nanoparticles into a chitosan/gelatin(Cs/Gel)matrix.The physical and chemical properties of the Cs/Gel/PHA scafold with 0–10 wt%PBT were analyzed.Cell and animal experiments were performed to characterize the immunomodulatory,angiogenic,and osteogenic capabilities of the piezoelectric hydrogel scafold in vitro and in vivo.Results:The incorporation of BaTiO_(3) into the scafold improved its mechanical properties and increased self-generated electricity.Due to their endogenous piezoelectric stimulation and bioactive constituents,the prepared Cs/Gel/PHA/PBT hydrogels exhibited cytocompatibility as well as immunomodulatory,angiogenic,and osteogenic capabilities;they not only effectively induced macrophage polarization to M2 phenotype but also promoted the migration,tube formation,and angiogenic differentiation of human umbilical vein endothelial cells(HUVECs)and facilitated the migration,osteodifferentiation,and extracellular matrix(ECM)mineralization of MC3T3-E1 cells.The in vivo evaluations showed that these piezoelectric hydrogels with versatile capabilities significantly facilitated new bone formation in a rat large-sized cranial injury model.The underlying molecular mechanism can be partly attributed to the immunomodulation of the Cs/Gel/PHA/PBT hydrogels as shown via transcriptome sequencing analysis,and the PI3K/Akt signaling axis plays an important role in regulating macrophage M2 polarization.Conclusion:The piezoelectric Cs/Gel/PHA/PBT hydrogels developed here with favorable immunomodulation,angiogenesis,and osteogenesis functions may be used as a substitute in periosteum injuries,thereby offering the novel strategy of applying piezoelectric stimulation in bone tissue engineering for the enhancement of combat efectiveness in grassroots troops.
文摘Cumulative evidence suggests that O-linkedβ-N-acetylglucosaminylation(OGlcNAcylation)plays an important regulatory role in pathophysiological processes.Although the regulatory mechanisms of O-GlcNAcylation in tumors have been gradually elucidated,the potential mechanisms of O-GlcNAcylation in bone metabolism,particularly,in the osteogenic differentiation of bone marrow mesenchymal stromal cells(BMSCs)remains unexplored.In this study,the literature related to O-GlcNAcylation and BMSC osteogenic differentiation was reviewed,assuming that it could trigger more scholars to focus on research related to OGlcNAcylation and bone metabolism and provide insights into the development of novel therapeutic targets for bone metabolism disorders such as osteoporosis.
文摘BACKGROUND Regular physical activity during childhood and adolescence is beneficial to bone development,as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.AIM To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms.METHODS 20 growing mice were randomly divided into two groups:Con group(control group,n=10)and Ex group(treadmill exercise group,n=10).Hematoxylin-eosin staining,immunohistochemistry,and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur.Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19(lncRNA H19).RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation.RESULTS Compared with the Con group,the expression of bone morphogenetic protein 2 was also significantly increased.The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density,bone volume fraction,and the number of trabeculae,and decreased trabecular segregation in the femur of mice.Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation.In addition,knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers,which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence.CONCLUSION Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice,thus enhancing the peak bone mass of mice.The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.
文摘Introduction: Solitary exostoses are the most common benign tumors of the fertile metaphyses of the long bones of children. Their radiological diagnosis of metaphyseal bone growth must be confirmed on pathological examination. These tumors can remain asymptomatic for a long time and reveal themselves during a particularly vascular complication. The objective of this study was to describe the epidemiological, diagnostic, therapeutic and evolutionary aspects of these tumors. Patient and Observation: We report the case of a 15-year-old adolescent girl, with no particular pathological history, received in the pediatric surgery department of the Donka National Hospital (HND) of the Conakry University Hospital for recurrent acute painful swelling of the lower third of the left thigh in an afebrile context accompanied by lameness and stopping school for a few days (2 - 3 days). The symptoms appear to have evolved over the past 3 years and after physical activities. It regresses with rest, analgesics and non-steroidal anti-inflammatory drugs. The notion of trauma and sickle cell disease was not reported in the patient's clinical history. It is the persistence of the symptomatology which motivates the said consultation. On palpation, a small hard mass is noted at the expense of the internal metaphysis of the left distal femur. Deep palpation of this area causes a tingling sensation and during rapid mobilization of the knee. The remainder of the orthopedic examination was unremarkable. Standard x-ray of the femur shows a bony growth with a pointed tip from the distal metaphysis of the left femur. On surgical exploration, we noted a wedge-shaped exostosis oriented towards the vastus medialis muscle. Histological examination of the surgical specimen confirms osteogenic exostosis. There is no recurrence after 2 years. Conclusion: The distal femoral metaphysis is the most common location of solitary osteochondromas in children. Their definitive diagnosis requires the histology of the surgical specimen. Only symptomatic exostoses should be operated on in children.
基金supported by the National Nature Science Foundation of China(Nos.51861145311,22005338)Science Foundation of China University of Petroleum,Beijing(No.2462017YJRC027)Open Project of State Key Laboratory of Superhard Materials(Jilin University 201802)。
文摘For bone regenerative engineering,it is a promising method to form skeletal tissues differentiating from human bone morrow mesenchyme stem cells(hBMSCs).However,it is still a critical challenge to efficiently control ostogenesis and clearly reveal the influence factor.To this end,the fluorescent gold nanodots(Au NDs) with highly negative charges as osteogenic induction reagent are successfully synthesized,which display better than commercial osteogenic induction medium through the investigations of ALP activity(2.5 folds) and cytoskeleton staining(1.5 folds).Two kinds of oligopeptides with different bio-structures(cysteine,Cys and glutathione,GSH) are selected for providing surficial charges on Au NDs.It is revealed that Au-Cys with more negative charges(-51 mV) play better role than Au-GSH(-19 mV) in osteogenic differentiation,when both of them have same size(~2 nm),sphere shape and show similar cell uptake amount.To explore deeply,osteogenesis related signaling pathways are monitored,revealing that the enhancement of osteogenic differentiation was through autophagy signaling pathway triggered by Au-Cys.And the promotion of highly negative charges in osteogenic diffe rentiation was further proved via sliver nanodots(Ag NDs,Ag-Cys and Ag-GSH) and carbon nanodots(CDs,Cys-CDs and GSH-CDs).This work indicates part of insights during hBMSCs differentiation and provides a novel strategy in osteogenic differentiation process.
基金supported by the National Basic Research Program (973) of China(No.2005CB623900)
文摘Objective:Large segmental bone defect repair remains a clinical and scientific challenge with increasing interest focusing on combining gene transfection with tissue engineering techniques.The aim of this study is to investigate the effect of connective tissue growth factor(CTGF) on the proliferation and osteogenic differentiation of the bone marrow mesenchymal stem cells(MSCs).Methods:A CTGF-expressing plasmid(pCTGF) was constructed and transfected into MSCs.Then expressions of bone morphogenesis-related genes,proliferation rate,alkaline phosphatase activity,and mineralization were examined to evaluate the osteogenic potential of the CTGF gene-modified MSCs.Results:Overexpression of CTGF was confirmed in pCTGF-MSCs.pCTGF transfection significantly enhanced the proliferation rates of pCTGF-MSCs(P<0.05).CTGF induced a 7.5-fold increase in cell migration over control(P<0.05).pCTGF transfection enhanced the expression of bone matrix proteins,such as bone sialo-protein,osteocalcin,and collagen type I in MSCs.The levels of alkaline phosphatase(ALP) activities of pCTGF-MSCs at the 1st and 2nd weeks were 4.0-and 3.0-fold higher than those of MSCs cultured in OS-medium,significantly higher than those of mock-MSCs and normal control MSCs(P<0.05).Overexpression of CTGF in MSCs enhanced the capability to form mineralized nodules.Conclusion:Overexpression of CTGF could improve the osteogenic differentiation ability of MSCs,and the CTGF gene-modified MSCs are potential as novel cell resources of bone tissue engineering.
基金Supported by National Natural Science Foundation of ChinaNo.81600882 and 81870755+4 种基金China Postdoctoral Science FoundationNo. 2019M663009President Foundation of Nanfang HospitalSouthern Medical UniversityNo.2019B002.
文摘Periodontal diseases are infectious diseases that are characterized by progressive damage to dental support tissue.The major goal of periodontal therapy is to regenerate the periodontium destroyed by periodontal diseases.Human periodontal ligament(PDL)tissue possesses periodontal regenerative properties,and periodontal ligament stem cells(PDLSCs)with the capacity for osteogenic differentiation show strong potential in clinical application for periodontium repair and regeneration.Noncoding RNAs(ncRNAs),which include a substantial portion of poly-A tail mature RNAs,are considered“transcriptional noise.”Recent studies show that ncRNAs play a major role in PDLSC differentiation;therefore,exploring how ncRNAs participate in the osteogenic differentiation of PDLSCs may help to elucidate the underlying mechanism of the osteogenic differentiation of PDLSCs and further shed light on the potential of stem cell transplantation for periodontium regeneration.In this review paper,we discuss the history of PDLSC research and highlight the regulatory mechanism of ncRNAs in the osteogenic differentiation of PDLSCs.
基金Supported by Natured Science Foundation of Anhui Province,No.1908085MH255.
文摘BACKGROUND In the clinical scenario,adult patients with periodontal diseases and dental malformation,characterized by dental crowding in lower anterior teeth with the thin biotype,often require orthodontic treatment.This case report aimed to evaluate the clinical and radiographic outcomes of periodontally accelerated osteogenic orthodontics(PAOO)combined with autologous platelet-rich fibrin(PRF)in an adult patient with class I malocclusion along with dental crowding,a thin periodontal biotype,and buccal plate deficiency.CASE SUMMARY A 32-year-old female complaining of dental crowding and gingival bleeding was referred to the orthodontic clinic.The patient underwent periodontal risk assessment prior to orthodontic treatment.She was diagnosed with a high risk of gingival recession due to dental crowding,root prominence,loss of buccal plates,and a thin gingival tissue biotype.The treatment regimen included PAOO combined with autologous PRF for alveolar augmentation and interproximal enamel reduction for moderate dental crowding.Clinically,PAOO-assisted orthodontic tooth movement in this case showed enhanced periodontium remodeling.Radiographic outcomes also showed statistically significant improvements(P<0.01)in the mandibular buccal alveolar bone.CONCLUSION This case report suggests the combination of autologous PRF with PAOO to enhance bone augmentation and long-term tissue support in adult orthodontic patients with periodontal disease.
基金financially supported by InterGovernmental S&T Cooperation Project Between China and Romania (2018LMNY003)Sichuan Science and Technology Innovation Team of China (2019JDTD0008)the Fundamental Research Funds for the Central Universities (2021SCU12071)。
文摘The rapid degradation of magnesium(Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. In the present study, three Mg alloys, including Mg-0.8Ca(denoted as ZQ), Mg-0.8Ca-5Zn-1.5Ag(denoted as ZQ71) and Mg-0.8Ca-5Zn-2.5Ag(denoted as ZQ63), were fabricated by alloying with calcium(Ca), zinc(Zn) and silver(Ag). The results obtained from electrochemical corrosion tests and in vitro degradation evaluation demonstrated that the three Mg alloys exhibited distinct corrosion resistance, and ZQ71 exhibited the lowest degradation rate in vitro among them. After addition of Zn and Ag, the antibacterial potential of Mg alloys was also enhanced. The in vitro cell experiments showed that all the three Mg alloys had good biocompatibility. After implantation in a rat femoral defect, ZQ71 showed significantly higher osteogenic activity and bone substitution rate than ZQ63 and ZQ, due to its higher corrosion resistance as well as the stimulatory effects of the released metallic ions. In addition, the average daily degradation rate of each Mg alloy in vivo was significantly higher than that in vitro, as could be due to the implantation site located in the highly vascularized trabecular region. Importantly, the correlations between the in vitro and in vivo degradation parameters of the Mg alloys were systematically analyzed to find out the potential predictors of the in vivo degradation performance of the materials. The current work not only evaluated the clinical potential of the three biodegradable Mg alloys as bone grafts but also provided a feasible approach for predicting the in vivo degradation behavior of biodegradable materials.
