Kawai Masanobu
Department of Bone and Mineral Research, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Izumi, Osaka, Japan.
Horm Mol Biol Clin Investig. 2013 Sep;15(3):105-13. doi: 10.1515/hmbci-2013-0036.
Peroxisome proliferator-activated receptor-γ (PPARγ) is a critical factor for the reciprocal regulation of adipogenesis and osteogenesis. Because of their insulin-sensitizing effect, PPARγ agonists, the thiazolidinediones (TZDs), have been widely used for the treatment of type 2 diabetes mellitus; however, the use of TZDs has also been revealed to cause bone loss and bone fractures. The nodal point of regulation of skeletal metabolism by PPARγ activation may reside in its role in cell fate determination of mesenchymal stem cells toward adipogenesis at the expense of osteogenesis. In addition, accumulating evidence demonstrates that PPARγ possesses a circadian expression profile and plays an important role in the skeletal and adipose metabolism regulated by the circadian clock network. Recently, we have shown that nocturnin, a circadian-regulated gene, enhances PPARγ activity, resulting in the suppression of osteogenesis and enhancement of adipogenesis, thus providing additional evidence of the link between circadian networks and PPARγ. In this review, we will focus on the emerging concept of PPARγ as a regulator for skeletal metabolism and summarize recent findings about one of the mechanisms on how PPARγ is connected to the circadian-regulatory system, which involves nocturnin.
过氧化物酶体增殖物激活受体γ（PPARγ）是脂肪生成和成骨相互调节的关键因子。由于噻唑烷二酮类（TZDs）具有胰岛素增敏作用，PPARγ激动剂已被广泛用于治疗2型糖尿病；然而，使用TZDs也被发现会导致骨质流失和骨折。PPARγ激活调节骨骼代谢的关键点可能在于其在间充质干细胞向脂肪生成而非成骨的细胞命运决定中的作用。此外，越来越多的证据表明，PPARγ具有昼夜节律表达模式，并在昼夜节律时钟网络调节的骨骼和脂肪代谢中发挥重要作用。最近，我们发现昼夜节律调节基因夜蛋白增强了PPARγ的活性，导致成骨抑制和脂肪生成增强，从而为昼夜节律网络与PPARγ之间的联系提供了更多证据。在这篇综述中，我们将重点关注PPARγ作为骨骼代谢调节因子这一新兴概念，并总结关于PPARγ如何与昼夜节律调节系统相连的其中一种机制的最新研究结果，这一机制涉及夜蛋白。
