过氧化物酶体增殖物激活受体γ及其激动剂噻唑烷二酮类药物对骨骼成骨的影响及作用机制

过氧化物酶体增殖物激活受体γ(PPARγ)及配体是影响骨髓间充质干细胞分化与成熟的重要调控因子,可通过降低骨钙素、骨形成蛋白2等成骨细胞特异性成熟因子的表达,抑制成骨细胞的分化,亦可诱导成骨细胞的凋亡,最终导致骨丢失。目前普遍认为PPARγ参与了老年性骨质疏松、绝经后骨质疏松和继发性骨质疏松的发生、发展。PPARγ激动剂噻唑烷二酮类药物(TZDs)因其导致骨量降低、增加骨折发生率而备受争议,通过化学结构修饰将有可能避免这一不良反应发生。

Influence and mechainsm of peroxisome proliferator activated receptor gamma and its agonists thiazolidinediones for osteogenesis

Peroxisome proliferator activated receptor(PPAR) 7 and its ligands are the important regulatory factors which influence the differentiation of bone marrow mesenchymal stem cells(MSCs).It can restrain the differentiation and maturity of osteoblasts through down-regulating the expression of the specificity mature factor,such as osteocalcin(OCN),bone morphogenetic protein(BMP)-2 and so on.It also can induce the apoptosis of osteoblasts,eventually lead to bone loss.There is broad agreement that PPAR 7 involved in the initiation and development of osteoporosis,such as senile osteoporosis,postmenopausal osteoporosis and secondary osteoporosis.PPAR7 agonists thiazolidinediones(TZDs) are now being disputed warmly because it contributes to the bone density declined and the risk of fracture increase.The adverse reactions would be avoided through the chemical structural modification of TZDs.