BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteo...BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.展开更多
The lifetime of roll-bits with inserted tooth will be obviously decreased while drilling in strata and the tungsten carbide can be integrally separated from the roll-cone,which will need more trip out time to replace ...The lifetime of roll-bits with inserted tooth will be obviously decreased while drilling in strata and the tungsten carbide can be integrally separated from the roll-cone,which will need more trip out time to replace the roller bit.This study provides an entire analysis on stress as well as strength for teeth and tooth holes in loaded conditions.Qualities of tooth drop from matrix within roller bit.The optimized interferences of teeth inserted into the bit can be reasonably obtained by the critical interference derived from some relevant influence factors on the tooth-fixing quality of roller bits.展开更多
The oxygen isotope ratios （δ18O） preserved in marine sediments have been widely used to reconstruct past ocean temperatures. However, there remain significant uncertainties associated with this method, owing to ass...The oxygen isotope ratios （δ18O） preserved in marine sediments have been widely used to reconstruct past ocean temperatures. However, there remain significant uncertainties associated with this method, owing to assumptions about the δ18O of ancient seawater which affects the temperature inferred from sediment δ18O records. In this study, oxygen isotope compositions of phosphate in teeth and bones from five different modem cetacean species, including sperm whale, pygmy sperm whale, short-finned pilot whale, killer whale, and Cuvier＇s beaked whale, and three fossil whales were determined. The data were used to assess whether the oxygen isotope ratios of biogenic phosphate （δ18Op） from cetaceans are a reliable proxy for the oxygen isotopic composition of ocean water （δ18Ow）. The δ18Op values of modem cetaceans range from 15.5 ‰ to 21.3 ‰, averaging （19.6 ‰ ±0.8 ‰） （n = 136）.Using a greatly expanded global cetacean δ18Op dataset, the following regression equation is derived for cetaceans： δ18Ow = 0.95317 （4-0.03293） δ18Op- 17.971 （＋0.605）, r = 0.97253. The new equation, when applied to fossil teeth and bones, yielded reasonable estimates of ancient seawater δ18Ow values. Intra-tooth isotopic variations were observed within individual teeth. Among the selected species, the killer whale （O. orca） has largest intra-tooth δ18Op preference and migratory the lowest δ18Op values and the variation, reflecting its habitat behavior. The results show that oxygen isotope analysis of phosphate in cetacean teeth and dense ear bones provides a useful tool for reconstructing the oxygen isotopic composition of seawater and for examining environmental preferences （including migratory behavior） of both modem and ancient whales.展开更多
AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth(SHED) transplanted for bone regeneration in the dog mandibular defect.METHODS: In this prospective comparative study, SHEDs had been i...AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth(SHED) transplanted for bone regeneration in the dog mandibular defect.METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-andthrough defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level.RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue(P = 0.248), woven bone(P = 0.248) and compact bone(P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period.CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs.展开更多
BACKGROUND Tooth defects can cause elongation of occlusal teeth,leading to insufficient repair space.The combination of dental implant restoration and orthodontic treatment of oblique adjacent teeth has a significant ...BACKGROUND Tooth defects can cause elongation of occlusal teeth,leading to insufficient repair space.The combination of dental implant restoration and orthodontic treatment of oblique adjacent teeth has a significant therapeutic effect.AIM To explore clinical efficacy,bone density,and follow-up of implant and orthodontic treatment for patients with inclined adjacent teeth.METHODS In total,98 patients with oblique adjacent teeth were randomly assigned to implant restoration combined with orthodontic treatment(group A,n=49)or to receive implant restoration alone(group B,n=49).Changes in alveolar ridge bone density and apical bone density were observed before and after treatment in the two groups.Changes in chewing function and language function were compared between the two groups of patients.Follow-up lasted for 12 mo after repair to observe any adverse reactions in the oral cavity.RESULTS The clinical effective rates of group A and group B were 97.96%and 85.71%,respectively,with group A having a higher clinical effective rate than group B.After treatment,the bone density of the alveolar ridge and apical bone in both groups decreased compared to before treatment,while the chewing and language functions improved.The changes in various indicators in group A were more significant.After treatment,the satisfaction rate of group A(97.96%)was higher than that of group B(79.59%).The incidence of adverse reactions in group A(2.04%)was lower than that in group B(24.49%).CONCLUSION The amalgamation of implant restoration and orthodontic treatment for adjacent tilted teeth demonstrates notable clinical efficacy,diminishes alveolar bone resorption,and fosters patient functional rehabilitation while exhibiting negligible adverse reactions.展开更多
Bone morphogenetic proteins(BMPs) play a critical role in the growth and steroidogenesis of granulosa cells(GCs).BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors.Upon ligand binding...Bone morphogenetic proteins(BMPs) play a critical role in the growth and steroidogenesis of granulosa cells(GCs).BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors.Upon ligand binding,BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types.The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs.A strategy of RNA interference(RNAi)-mediated 'gene silencing' of Smad4,a core molecule mediating the intracellular BMP/Smad signal transduction pathways,was used to interrupt endogenous BMP/Smad signaling.Results indicate that Smad4-small interfering RNA(siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection.Interrupted endogenous BMP/Smad signaling significantly inhibited growth,and induced apoptosis of porcine GCs,while decreasing estradiol production.In addition,interrupted BMP/Smad signaling significantly(P<0.05) changed the expression of Cyclin D2,CDK4,Bcl-2,and Cyp19a1.These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.展开更多
Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the mo...Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.展开更多
Electron Spin Resonance (ESR) dating is a relatively new technique applicable also to the dating of materials from littoral zones and shallow sea regions, such as shells, corals, bones and teeth, foraminifera, diatoms...Electron Spin Resonance (ESR) dating is a relatively new technique applicable also to the dating of materials from littoral zones and shallow sea regions, such as shells, corals, bones and teeth, foraminifera, diatoms, etc. ESR dating can span the time interval between the older limit of 14C dating and the younger limit of the K-Ar dating, an interval of 103-106 years. Therefore, ESR technique is very suitaHe for the measurement of the age of Quaternary sea-level changes. This paper gives some samples’ results by ESR dating from Early Pleistoncene to Holocene.The Quaternary sea-level changes in China were mainly eustatisms that corresponded to the paleotemperature variation. We have just begun study on the 18O Paleotemperature in our continental area. Preliminary results show the temperature curve of the stalagmitic growth in caves corresponds well to the sea - level changes in 76-55×103 years B. P. ESR dating and studies of the 18O Paleotemperature in East China will raise studies on Quaternary sea -展开更多
BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),off...BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),offer promise due to their osteogenic and immunomodulatory potential.Sclerostin(SOST)inhibits bone formation,so we developed a multi-target gene silencing strategy against SOST using RNA interference.We created hUCMSCs with SOST-silenced(sh-hUCMSCs)and compared their therapeutic efficacy with unmodified hUCMSCs in SANFH mice.This study explores a novel approach to enhance osteogenesis and mitigate SANFH progression.AIM To assess the effects of sh-hUCMSCs on bone metabolism in SANFH.METHODS hUCMSCs were isolated from placental tissue and transfected with SOST-targeting short hairpin RNA plasmids.A SANFH mouse model was established through intraperitoneal injection of lipopolysaccharide(20μg/kg)followed by intramuscular methylprednisolone administration(40 mg/kg).Mice were randomized into four experimental groups(n=10/group):Sham control,SANFH(untreated),hUCMSCs-treated,and sh-hUCMSCs-treated.Micro-computed tomography was used to measure bone volume(BV),bone surface area,bone surface/BV ratio,tra-becular number,trabecular thickness,and trabecular separation.Quantification of adipocyte area by hematoxylin and eosin staining.Collagen fiber volume was assessed by Masson’s trichrome staining.Serum levels of osteopro-tegerin(OPG),receptor activator of nuclear factor kappa B(RANK),RANK ligand(RANKL),tartrate-resistant acid phosphatase,and the OPG/RANKL ratio were measured by enzyme-linked immunosorbent assay.The expression levels of alkaline phosphatase,OPG,SOST,β-catenin,peroxisome proliferator-activated receptor gamma,and CCAAT/enhancer-binding protein in bone tissue were determined by western blot analysis.RESULTS hUCMSCs and sh-hUCMSCs exhibited typical fibroblast-like morphology and high expression of MSC surface markers(CD90,CD73,CD105>98%).These cells demonstrated tri-lineage differentiation potential,confirmed by positive Alizarin Red S,Oil Red O,and Alcian Blue staining,and upregulation of lineage-specific genes.After SOST-RNA interference modification,sh-hUCMSCs showed enhanced inhibition of adipogenesis and improved bone formation in a rat model of SANFH.Histological analysis revealed reduced lipid infiltration and empty lacunae in the femoral head of the sh-hUCMSC group.Western blot showed decreased CCAAT/enhancer-binding protein and peroxisome proliferator-activated receptor gamma expression(P<0.05).Masson staining and micro-computed tomography analysis confirmed significantly increased BV,trabecular number,trabecular thickness,and reduced trabecular separation in the sh-hUCMSC group compared to unmodified MSCs and SANFH groups(P<0.05).Serum enzyme-linked immunosorbent assay showed higher OPG and lower RANK,RANKL,and tartrate-resistant acid phosphatase levels in the sh-hUCMSCs group.Western blot further confirmed upregulated alkaline phosphatase,OPG,β-catenin,and downregulated SOST expression in sh-hUCMSCs compared to controls(P<0.05).These results suggest that SOST inhibition enhances the osteogenic potential and therapeutic efficacy of hUCMSCs in SANFH.CONCLUSION sh-hUCMSCs alleviate SANFH by activating the Wnt/β-catenin signaling pathway,thereby promoting osteogenic differentiation and suppressing adipogenesis to restore bone metabolic balance.展开更多
目的探讨牙槽突扩张术(alveolar ridge expansion,ARE)联合骨引导再生植骨术(guided bone regenera-tion,GBR)同期种植牙在青少年牙齿发育异常中的临床应用效果。方法目的选取2021年1月—2023年12月淄博市中心医院收治的90例牙齿发育异...目的探讨牙槽突扩张术(alveolar ridge expansion,ARE)联合骨引导再生植骨术(guided bone regenera-tion,GBR)同期种植牙在青少年牙齿发育异常中的临床应用效果。方法目的选取2021年1月—2023年12月淄博市中心医院收治的90例牙齿发育异常的青少年为研究对象,按照不同治疗方式分为两组,每组45例。对照组采用牙槽骨劈开术(alveolar bone splitting,ABS)联合同期种植牙治疗;观察组则采用ARE联合GBR同期种植牙治疗。对比两组手术相关指标、种植体周围软组织情况及并发症发生率。结果观察组手术时间、离院时间及骨愈合时间均短于对照组,差异均有统计学意义(P均<0.05)。治疗6个月后,观察组种植体周围软组织情况优于对照组,差异均有统计学意义(P均<0.05)。且观察组并发症发生率为4.44%(2/45)低于对照组的17.78%(8/45),差异有统计学意义(χ^(2)=4.050,P<0.05)。结论ARE联合GBR同期种植牙在青少年牙齿发育异常的治疗中,相较于ABS联合同期种植牙,能够显著缩短治疗周期,改善种植体周围软组织状况,并降低术后并发症发生率,是一种更为有效且安全的治疗方法。展开更多
基金Supported by the National Natural Science Foundation of China,No.82160192and Guangxi Science and Technology Program,No.2023AB23037.
文摘BACKGROUND In vivo degradation of bone scaffolds is significantly influenced by osteoclast(OC)activity,which is orchestrated by the interplay between receptor activator of nuclear factor-kappa B ligand(RANKL)and osteoprotegerin(OPG).The ratio of RANKL/OPG is a crucial determinant of OC-mediated bone resorption,which plays an integral role in bone remodeling and scaffold degradation.Elevated levels of RANKL relative to OPG enhance osteoclastogenesis,thereby accelerating the degradation process essential for integrating bone scaffolds into the host tissue.AIM To elucidate the effects of OPG gene silencing on osteoclastogenesis within rat bone marrow-derived mesenchymal stem cells(BMSCs).By investigating these effects,the study aimed to provide deeper insights into the regulatory mechanisms that influence bone scaffold degradation,potentially leading to improved bone repair and regeneration strategies.METHODS We employed recombinant lentiviral plasmids to silence the OPG gene in rat BMSCs to achieve the aims.The efficacy of gene silencing was assessed using quantitative reverse transcription polymerase chain reaction and western blot analysis to measure the expression levels of OPG and RANKL.Tartrate-resistant acid phosphatase staining was utilized to evaluate the formation of OCs.Additionally,co-immunoprecipitation assays were conducted to explore the interactions between RANKL and OPG proteins,further assessing the biochemical pathways involved in osteoclastogenesis.RESULTS The silencing of the OPG gene in BMSCs resulted in a significant increase in the RANKL/OPG ratio,evidenced by decreased expression levels of OPG and increased levels of RANKL.Enhanced osteoclastogenesis was observed through tartrate-resistant acid phosphatase staining,which indicated a substantial rise in OC formation in response to the altered RANKL/OPG balance.The co-immunoprecipitation assays provided concrete evidence of the direct interaction between RANKL and OPG proteins,substantiating their pivotal roles in regulating OC activity.CONCLUSION The findings from this study underscore the critical role of the RANKL/OPG axis in osteoclastogenesis.Silencing of the OPG gene in BMSCs effectively increases the RANKL/OPG ratio,promoting OC activity and potentially enhancing bone scaffold degradation.This regulatory mechanism offers a promising avenue for modulating bone remodeling processes,which is essential for effective bone repair and the successful integration of bone scaffolds into damaged sites.Future research might focus on optimizing the control of this axis to better facilitate bone tissue engineering and regenerative therapies.
文摘The lifetime of roll-bits with inserted tooth will be obviously decreased while drilling in strata and the tungsten carbide can be integrally separated from the roll-cone,which will need more trip out time to replace the roller bit.This study provides an entire analysis on stress as well as strength for teeth and tooth holes in loaded conditions.Qualities of tooth drop from matrix within roller bit.The optimized interferences of teeth inserted into the bit can be reasonably obtained by the critical interference derived from some relevant influence factors on the tooth-fixing quality of roller bits.
基金supported by US National Science Foundation Cooperative Agreement No.DMR-1157490 and the State of Floridathe State of Florida.The Stable Isotope Lab was established with grants from the US National Science Foundation(EAR-0824628EAR-0517806 and EAR-0236357)
文摘The oxygen isotope ratios （δ18O） preserved in marine sediments have been widely used to reconstruct past ocean temperatures. However, there remain significant uncertainties associated with this method, owing to assumptions about the δ18O of ancient seawater which affects the temperature inferred from sediment δ18O records. In this study, oxygen isotope compositions of phosphate in teeth and bones from five different modem cetacean species, including sperm whale, pygmy sperm whale, short-finned pilot whale, killer whale, and Cuvier＇s beaked whale, and three fossil whales were determined. The data were used to assess whether the oxygen isotope ratios of biogenic phosphate （δ18Op） from cetaceans are a reliable proxy for the oxygen isotopic composition of ocean water （δ18Ow）. The δ18Op values of modem cetaceans range from 15.5 ‰ to 21.3 ‰, averaging （19.6 ‰ ±0.8 ‰） （n = 136）.Using a greatly expanded global cetacean δ18Op dataset, the following regression equation is derived for cetaceans： δ18Ow = 0.95317 （4-0.03293） δ18Op- 17.971 （＋0.605）, r = 0.97253. The new equation, when applied to fossil teeth and bones, yielded reasonable estimates of ancient seawater δ18Ow values. Intra-tooth isotopic variations were observed within individual teeth. Among the selected species, the killer whale （O. orca） has largest intra-tooth δ18Op preference and migratory the lowest δ18Op values and the variation, reflecting its habitat behavior. The results show that oxygen isotope analysis of phosphate in cetacean teeth and dense ear bones provides a useful tool for reconstructing the oxygen isotopic composition of seawater and for examining environmental preferences （including migratory behavior） of both modem and ancient whales.
文摘AIM: To investigate the effect of stem cells from human exfoliated deciduous teeth(SHED) transplanted for bone regeneration in the dog mandibular defect.METHODS: In this prospective comparative study, SHEDs had been isolated 5 years ago from human exfoliated deciduous teeth. The undifferentiated stem cells were seeded into mandibular bone through-andthrough defects of 4 dogs. Similar defects in control group were filled with cell-free collagen scaffold. After 12 wk, biopsies were taken and morphometric analysis was performed. The percentage of new bone formation and foreign body reaction were measured in each case. The data were subject to statistical analysis using the Mann-Whitney U and Kruskalwalis statistical tests. Differences at P < 0.05 was considered as significant level.RESULTS: There were no significant differences between control and SHED-seeded groups in connective tissue(P = 0.248), woven bone(P = 0.248) and compact bone(P = 0.082). There were not any side effects in transplanted SHED group such as teratoma or malignancy and abnormalities in this period.CONCLUSION: SHEDs which had been isolated and characterized 5 years ago and stored with cryopreservation banking were capable of proliferation and osteogenesis after 5 years, and no immune response was observed after three months of seeded SHEDs.
基金the Review Committee of General Hospital of Central Theater Command(Approval No.05901).
文摘BACKGROUND Tooth defects can cause elongation of occlusal teeth,leading to insufficient repair space.The combination of dental implant restoration and orthodontic treatment of oblique adjacent teeth has a significant therapeutic effect.AIM To explore clinical efficacy,bone density,and follow-up of implant and orthodontic treatment for patients with inclined adjacent teeth.METHODS In total,98 patients with oblique adjacent teeth were randomly assigned to implant restoration combined with orthodontic treatment(group A,n=49)or to receive implant restoration alone(group B,n=49).Changes in alveolar ridge bone density and apical bone density were observed before and after treatment in the two groups.Changes in chewing function and language function were compared between the two groups of patients.Follow-up lasted for 12 mo after repair to observe any adverse reactions in the oral cavity.RESULTS The clinical effective rates of group A and group B were 97.96%and 85.71%,respectively,with group A having a higher clinical effective rate than group B.After treatment,the bone density of the alveolar ridge and apical bone in both groups decreased compared to before treatment,while the chewing and language functions improved.The changes in various indicators in group A were more significant.After treatment,the satisfaction rate of group A(97.96%)was higher than that of group B(79.59%).The incidence of adverse reactions in group A(2.04%)was lower than that in group B(24.49%).CONCLUSION The amalgamation of implant restoration and orthodontic treatment for adjacent tilted teeth demonstrates notable clinical efficacy,diminishes alveolar bone resorption,and fosters patient functional rehabilitation while exhibiting negligible adverse reactions.
基金(No. 2006AA10Z136) supported by National High-Tech R & D Program (863) of China
文摘Bone morphogenetic proteins(BMPs) play a critical role in the growth and steroidogenesis of granulosa cells(GCs).BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors.Upon ligand binding,BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types.The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs.A strategy of RNA interference(RNAi)-mediated 'gene silencing' of Smad4,a core molecule mediating the intracellular BMP/Smad signal transduction pathways,was used to interrupt endogenous BMP/Smad signaling.Results indicate that Smad4-small interfering RNA(siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection.Interrupted endogenous BMP/Smad signaling significantly inhibited growth,and induced apoptosis of porcine GCs,while decreasing estradiol production.In addition,interrupted BMP/Smad signaling significantly(P<0.05) changed the expression of Cyclin D2,CDK4,Bcl-2,and Cyp19a1.These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.
基金The reported work was supported in part by research grants from the National Institutes of Health(CA226303,DE020140 to TCH and RRR)the U.S.Department of Defense(OR130096 to JMW)+1 种基金the Chicago Biomedical Consortium with support from the Searle Funds at The Chicago Community Trust(RRR,TCH),the Scoliosis Research Society(TCH and MJL)the National Key Research and Development Program of China(2016YFC1000803 and 2011CB707906 to TCH).
文摘Mesenchymal stem cells(MSCs)are multipotent stem cells and capable of differentiating into multiple cell types including osteoblastic,chondrogenic and adipogenic lineages.We previously identified BMP9 as one of the most potent BMPs that induce osteoblastic differentiation of MSCs although exact molecular mechanism through which BMP9 regulates osteogenic differentiation remains to be fully understood.Here,we seek to develop a recombinant adenovirus system to optimally silence mouse BMP9 and then characterize the important role of BMP9 in osteogenic differentiation of MSCs.Using two different siRNA bioinformatic prediction programs,we design five siRNAs targeting mouse BMP9(or simB9),which are expressed under the control of the converging H1 and U6 promoters in recombinant adenovirus vectors.We demonstrate that two of the five siRNAs,simB9-4 and simB9-7,exhibit the highest efficiency on silencing exogenous mouse BMP9 in MSCs.Furthermore,simB9-4 and simB9-7 act synergistically in inhibiting BMP9-induced expression of osteogenic markers,matrix mineralization and ectopic bone formation from MSCs.Thus,our findings demonstrate the important role of BMP9 in osteogenic differentiation of MSCs.The characterized simB9 siRNAs may be used as an important tool to investigate the molecular mechanism behind BMP9 osteogenic signaling.Our results also indicate that recombinant adenovirus-mediated expression of siRNAs is efficient and sustained,and thus may be used as an effective delivery vehicle of siRNA therapeutics.
文摘Electron Spin Resonance (ESR) dating is a relatively new technique applicable also to the dating of materials from littoral zones and shallow sea regions, such as shells, corals, bones and teeth, foraminifera, diatoms, etc. ESR dating can span the time interval between the older limit of 14C dating and the younger limit of the K-Ar dating, an interval of 103-106 years. Therefore, ESR technique is very suitaHe for the measurement of the age of Quaternary sea-level changes. This paper gives some samples’ results by ESR dating from Early Pleistoncene to Holocene.The Quaternary sea-level changes in China were mainly eustatisms that corresponded to the paleotemperature variation. We have just begun study on the 18O Paleotemperature in our continental area. Preliminary results show the temperature curve of the stalagmitic growth in caves corresponds well to the sea - level changes in 76-55×103 years B. P. ESR dating and studies of the 18O Paleotemperature in East China will raise studies on Quaternary sea -
基金Supported by the National Natural Science Foundation of China,No.82260944the Key Research and Development Programs of Guangxi,No.2021AB09011。
文摘BACKGROUND Steroid-induced avascular necrosis of the femoral head(SANFH)involves bone metabolism imbalance and lacks effective therapies.Mesenchymal stem cells(MSCs),particularly human umbilical cord MSCs(hUCMSCs),offer promise due to their osteogenic and immunomodulatory potential.Sclerostin(SOST)inhibits bone formation,so we developed a multi-target gene silencing strategy against SOST using RNA interference.We created hUCMSCs with SOST-silenced(sh-hUCMSCs)and compared their therapeutic efficacy with unmodified hUCMSCs in SANFH mice.This study explores a novel approach to enhance osteogenesis and mitigate SANFH progression.AIM To assess the effects of sh-hUCMSCs on bone metabolism in SANFH.METHODS hUCMSCs were isolated from placental tissue and transfected with SOST-targeting short hairpin RNA plasmids.A SANFH mouse model was established through intraperitoneal injection of lipopolysaccharide(20μg/kg)followed by intramuscular methylprednisolone administration(40 mg/kg).Mice were randomized into four experimental groups(n=10/group):Sham control,SANFH(untreated),hUCMSCs-treated,and sh-hUCMSCs-treated.Micro-computed tomography was used to measure bone volume(BV),bone surface area,bone surface/BV ratio,tra-becular number,trabecular thickness,and trabecular separation.Quantification of adipocyte area by hematoxylin and eosin staining.Collagen fiber volume was assessed by Masson’s trichrome staining.Serum levels of osteopro-tegerin(OPG),receptor activator of nuclear factor kappa B(RANK),RANK ligand(RANKL),tartrate-resistant acid phosphatase,and the OPG/RANKL ratio were measured by enzyme-linked immunosorbent assay.The expression levels of alkaline phosphatase,OPG,SOST,β-catenin,peroxisome proliferator-activated receptor gamma,and CCAAT/enhancer-binding protein in bone tissue were determined by western blot analysis.RESULTS hUCMSCs and sh-hUCMSCs exhibited typical fibroblast-like morphology and high expression of MSC surface markers(CD90,CD73,CD105>98%).These cells demonstrated tri-lineage differentiation potential,confirmed by positive Alizarin Red S,Oil Red O,and Alcian Blue staining,and upregulation of lineage-specific genes.After SOST-RNA interference modification,sh-hUCMSCs showed enhanced inhibition of adipogenesis and improved bone formation in a rat model of SANFH.Histological analysis revealed reduced lipid infiltration and empty lacunae in the femoral head of the sh-hUCMSC group.Western blot showed decreased CCAAT/enhancer-binding protein and peroxisome proliferator-activated receptor gamma expression(P<0.05).Masson staining and micro-computed tomography analysis confirmed significantly increased BV,trabecular number,trabecular thickness,and reduced trabecular separation in the sh-hUCMSC group compared to unmodified MSCs and SANFH groups(P<0.05).Serum enzyme-linked immunosorbent assay showed higher OPG and lower RANK,RANKL,and tartrate-resistant acid phosphatase levels in the sh-hUCMSCs group.Western blot further confirmed upregulated alkaline phosphatase,OPG,β-catenin,and downregulated SOST expression in sh-hUCMSCs compared to controls(P<0.05).These results suggest that SOST inhibition enhances the osteogenic potential and therapeutic efficacy of hUCMSCs in SANFH.CONCLUSION sh-hUCMSCs alleviate SANFH by activating the Wnt/β-catenin signaling pathway,thereby promoting osteogenic differentiation and suppressing adipogenesis to restore bone metabolic balance.
文摘目的探讨牙槽突扩张术(alveolar ridge expansion,ARE)联合骨引导再生植骨术(guided bone regenera-tion,GBR)同期种植牙在青少年牙齿发育异常中的临床应用效果。方法目的选取2021年1月—2023年12月淄博市中心医院收治的90例牙齿发育异常的青少年为研究对象,按照不同治疗方式分为两组,每组45例。对照组采用牙槽骨劈开术(alveolar bone splitting,ABS)联合同期种植牙治疗;观察组则采用ARE联合GBR同期种植牙治疗。对比两组手术相关指标、种植体周围软组织情况及并发症发生率。结果观察组手术时间、离院时间及骨愈合时间均短于对照组,差异均有统计学意义(P均<0.05)。治疗6个月后,观察组种植体周围软组织情况优于对照组,差异均有统计学意义(P均<0.05)。且观察组并发症发生率为4.44%(2/45)低于对照组的17.78%(8/45),差异有统计学意义(χ^(2)=4.050,P<0.05)。结论ARE联合GBR同期种植牙在青少年牙齿发育异常的治疗中,相较于ABS联合同期种植牙,能够显著缩短治疗周期,改善种植体周围软组织状况,并降低术后并发症发生率,是一种更为有效且安全的治疗方法。
