Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone form...Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.展开更多
基金supported by the Excellent Young Scientist Foundation of the National Natural Science Foundation of China(Grant No.81522012)the National Natural Science Foundation of China(Grant No.81670807,81600699,81702237,81701383,81400858)+8 种基金the Thousand Youth Talents Plan of China(Grant No.D1119003)the Hunan Youth Talent Project(Grant No.2016RS3021)the Innovation Driven Project of Central South University(2016CX028)the Youth Foundation of Xiangya Hospital in Central South University(Grant No.2016Q10)the Fundamental Research Funds for the Central Universities of Central South University(Grant No.2017zzts032,2017zzts014)the Hunan Province Natural Science Foundation of China(Grant No.2017JJ3501)the China Postdoctoral Science Foundation(Grant No.2017M612596)the Natural Science Foundation for Distinguished Yong Scholars of Guangdong Province(2016A030306051)the National Basic Research Program of China(973 Program,Grant no.2014CB942903)
文摘Osteoporosis is a frequent complication of chronic inflammatory diseases and increases in the pro-inflammatory cytokines make an important contribution to bone loss by promoting bone resorption and impairing bone formation. Omentin-1 is a newly identified adipocytokine that has anti-inflammatory effects, but little is known about the role of omentin-1 in inflammatory osteoporosis. Here we generated global omentin-1 knockout（omentin-1^-/-） mice and demonstrated that depletion of omentin-1 induces inflammatory bone loss-like phenotypes in mice, as defined by abnormally elevated pro-inflammatory cytokines, increased osteoclast formation and bone tissue destruction, as well as impaired osteogenic activities. Using an inflammatory cell model induced by tumor necrosis factor-α（TNF-α）, we determined that recombinant omentin-1 reduces the production of proinflammatory factors in the TNF-α-activated macrophages, and suppresses their anti-osteoblastic and pro-osteoclastic abilities. In the magnesium silicate-induced inflammatory osteoporosis mouse model, the systemic administration of adenoviral-delivered omentin-1 significantly protects from osteoporotic bone loss and inflammation. Our study suggests that omentin-1 can be used as a promising therapeutic agent for the prevention or treatment of inflammatory bone diseases by downregulating the proinflammatory cytokines.
文摘目的观察不同体重指数2型糖尿病(type 2 diabetes mellitus,T2DM)患者血清脂肪细胞型脂肪酸结合蛋白4(fatty acid-binding protein 4,FABP4)、人网膜素-1(Omentin-1)的水平,探讨其与胰岛素抵抗的关系。方法选取127例住院治疗的T2DM患者,按体重指数分为T2DM体重正常组(42例)、超重组(44例)、肥胖组(41例),测定各组空腹血糖、血脂、空腹胰岛素、糖化血红蛋白等指标,采用酶联免疫吸附法分别检测血清FABP4、Omentin-1水平。利用HOMA模型计算胰岛素抵抗指数(HOMA of insulin resistance,HOMA-IR)。采用单因素方差分析(ANOVA)、Pearson相关分析、多元回归分析,探讨FABP4、Omentin-1与胰岛素抵抗的关系。结果分别与T2DM体重正常组、超重组比较,T2DM肥胖组患者FABP4、HOMA-IR水平均显著升高,Omentin-1水平显著降低(P<0.05)。Pearson相关分析显示,T2DM体重正常组、超重组、肥胖组中,FABP4(r=0.413、0.495、0.621,P<0.05)与HOMA-IR均呈显著正相关,Omentin-1(r=-0.509、-0.592、-0.675,P<0.05)与HOMA-IR呈显著负相关。多元逐步回归分析显示,FABP4、Omentin-1可能是影响胰岛素抵抗的独立危险因素。结论T2DM患者血清FABP4水平与胰岛素抵抗呈正相关,Omentin-1与胰岛素抵抗呈负相关;FABP4、Omentin-1可能是影响胰岛素抵抗的独立危险因素。
