Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health p...Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.展开更多
目的:观察青藤碱(SIN)联合甲氨蝶呤(MTX)治疗早期类风湿关节炎(RA)的疗效及对患者血清基质金属蛋白酶3(MMP-3)、核因子-κB受体活化因子配体(RANKL)/骨保护素(OPG)表达的影响。方法:纳入68例早期RA患者,按照随机数字表分为治疗组和对照...目的:观察青藤碱(SIN)联合甲氨蝶呤(MTX)治疗早期类风湿关节炎(RA)的疗效及对患者血清基质金属蛋白酶3(MMP-3)、核因子-κB受体活化因子配体(RANKL)/骨保护素(OPG)表达的影响。方法:纳入68例早期RA患者,按照随机数字表分为治疗组和对照组,每组各34例。对照组患者给予MTX治疗,治疗组患者给予MTX联合SIN治疗,两组疗程均为12周。采用美国风湿病学会(American College of Rheumatology,ACR)20、50、70标准评价两组患者的临床疗效,检测患者的类风湿因子(RF)、血沉(ESR)、C反应蛋白(CRP)及血清MMP-3、OPG、RANKL表达水平。结果:治疗后,治疗组的ACR 20、50、70达标率分别为76.7%、40.0%、3.3%,对照组分别为34.5%、20.7%、6.9%,治疗组的ACR 20达标率显著高于对照组(P<0.01)。治疗后,治疗组患者的RF、ESR、CRP水平均降低(P<0.01),对照组患者的RF、ESR、CRP水平与治疗前比较差异无统计学意义(P>0.05);且两组患者的ESR、CRP、RF水平治疗前后差值比较,差异均有统计学意义(P<0.01),治疗组患者上述指标的改善优于对照组。治疗后,治疗组患者的MMP-3、RANKL水平降低(P<0.01,P<0.05),OPG水平和OPG/RANKL比值升高(P<0.01,P<0.05);对照组患者的MMP-3水平亦降低(P<0.05);且两组患者的OPG、RANKL水平及OPG/RANKL比值治疗前后差值比较,差异均有统计学意义(P<0.01,P<0.05),治疗组患者上述指标的改善优于对照组。结论:SIN联合MTX可改善早期RA患者的临床症状,调控MMP-3及RANKL/OPG系统,这可能是其抑制骨侵蚀、促进骨保护的机制之一。展开更多
After it was suggested 30 years ago that the osteoblast lineage controlled the formation of osteoclasts, methods were developed that established this to be the case, but the molecular controls were elusive. Over more ...After it was suggested 30 years ago that the osteoblast lineage controlled the formation of osteoclasts, methods were developed that established this to be the case, but the molecular controls were elusive. Over more than a decade much evidence was obtained for signaling mechanisms that regulated the production of a membrane- bound regulator of osteoclastogenesis, in the course of which intercellular communication in bone was revealed in its complexity. The discovery of regulation by tumor necrosis factor ligand and receptor families was made in the last few years of the twentieth century, leading since then to a new physiology of bone, and to exciting drug development.展开更多
Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis(RA) patients. Recent progress in bone cel...Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis(RA) patients. Recent progress in bone cell biology has revealed the molecular mechanism of osteoclast differentiation and bone resorption by mature osteoclasts. We highlight here the potential role of the receptor activator of nuclear factor κB ligand(RANKL)-RANK pathways in bone destruction in RA and review recent clinical trials treating RA by targeting RANKL.展开更多
文摘Osteoporosis has become a serious health problem throughout the world which is associated with an increased risk of bone fractures and mortality among the people of middle to old ages.Diabetes is also a major health problem among the people of all age ranges and the sufferers due to this abnormality increasing day by day.The aim of this review is to summarize the possible mechanisms through which diabetes may induce osteoporosis.Diabetes mellitus generally exerts its effect on different parts of the body including bone cells specially the osteoblast and osteoclast,muscles,retina of the eyes,adipose tissue,endocrine system specially parathyroid hormone(PTH) and estrogen,cytokines,nervous system and digestive system.Diabetes negatively regulates osteoblast differentiation and function while positively regulates osteoclast differentiation and function through the regulation of different intermediate factors and thereby decreases bone formation while increases bone resorption.Some factors such as diabetic neuropathy,reactive oxygen species,Vitamin D,PTH have their effects on muscle cells.Diabetes decreases the muscle strength through regulating these factors in various ways and ultimately increases the risk of fall that may cause bone fractures.
文摘目的:观察青藤碱(SIN)联合甲氨蝶呤(MTX)治疗早期类风湿关节炎(RA)的疗效及对患者血清基质金属蛋白酶3(MMP-3)、核因子-κB受体活化因子配体(RANKL)/骨保护素(OPG)表达的影响。方法:纳入68例早期RA患者,按照随机数字表分为治疗组和对照组,每组各34例。对照组患者给予MTX治疗,治疗组患者给予MTX联合SIN治疗,两组疗程均为12周。采用美国风湿病学会(American College of Rheumatology,ACR)20、50、70标准评价两组患者的临床疗效,检测患者的类风湿因子(RF)、血沉(ESR)、C反应蛋白(CRP)及血清MMP-3、OPG、RANKL表达水平。结果:治疗后,治疗组的ACR 20、50、70达标率分别为76.7%、40.0%、3.3%,对照组分别为34.5%、20.7%、6.9%,治疗组的ACR 20达标率显著高于对照组(P<0.01)。治疗后,治疗组患者的RF、ESR、CRP水平均降低(P<0.01),对照组患者的RF、ESR、CRP水平与治疗前比较差异无统计学意义(P>0.05);且两组患者的ESR、CRP、RF水平治疗前后差值比较,差异均有统计学意义(P<0.01),治疗组患者上述指标的改善优于对照组。治疗后,治疗组患者的MMP-3、RANKL水平降低(P<0.01,P<0.05),OPG水平和OPG/RANKL比值升高(P<0.01,P<0.05);对照组患者的MMP-3水平亦降低(P<0.05);且两组患者的OPG、RANKL水平及OPG/RANKL比值治疗前后差值比较,差异均有统计学意义(P<0.01,P<0.05),治疗组患者上述指标的改善优于对照组。结论:SIN联合MTX可改善早期RA患者的临床症状,调控MMP-3及RANKL/OPG系统,这可能是其抑制骨侵蚀、促进骨保护的机制之一。
基金Supported by The National Health and Medical Research Council(Australia)the Victorian Government OIS Program
文摘After it was suggested 30 years ago that the osteoblast lineage controlled the formation of osteoclasts, methods were developed that established this to be the case, but the molecular controls were elusive. Over more than a decade much evidence was obtained for signaling mechanisms that regulated the production of a membrane- bound regulator of osteoclastogenesis, in the course of which intercellular communication in bone was revealed in its complexity. The discovery of regulation by tumor necrosis factor ligand and receptor families was made in the last few years of the twentieth century, leading since then to a new physiology of bone, and to exciting drug development.
文摘Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis(RA) patients. Recent progress in bone cell biology has revealed the molecular mechanism of osteoclast differentiation and bone resorption by mature osteoclasts. We highlight here the potential role of the receptor activator of nuclear factor κB ligand(RANKL)-RANK pathways in bone destruction in RA and review recent clinical trials treating RA by targeting RANKL.
