Involvement of PPAR γ in senescence-induced osteoporosis

衰老性骨质疏松症被认为是一种低周转率类型，是由成骨细胞生成向脂肪生成的转变引起的。在本研究中，我们研究了一些影响骨代谢的药物对脂肪分化的影响以及脂肪形成对破骨细胞和成骨细胞形成的影响。我们使用在实验室建立的小鼠成骨前细胞系和从骨髓中分离的人间充质干细胞。PPARγ配体如15-脱氧。-Δ 12,14- pgj2和曲格列酮刺激脂肪形成，而IL-11和维生素ink2抑制脂肪形成。脂肪细胞分化导致破骨细胞支持形成活性降低，但不影响成骨细胞的形成。在体内研究中也得到了类似的结果。将含有BMP-2和维生素K2的人间充质细胞接种于Matrigel后皮下移植至裸鼠，BMP-2使细胞分化为成骨细胞和脂肪细胞。维生素K2对成骨细胞的影响虽然有抑制脂肪生成的作用，但未被观察到。这些数据表明，抑制脂肪生成不利于保护衰老性骨质疏松症。

Senescence-induced osteoporosis is thought to be a low turnover type and to be due to the shift from osteoblastogenesis to adipogenesis. In this study, we investigated the effects of some drugs affected bone metabolism on adipose differentiation and the effects of adipogenesis on osteoclastogenesis and osteoblastogenesis. We used mouse preosteoblast cell lines established in our laboratory and human mesenchymal stem cells isolated from bone marrow. The PPARγ ligands such as 15-deoxy.-Δ 12,14-PGJ2 and trogritazone stimulated adipogenesis, but IL-11 and vitaminK2 suppressed the adipogenesis. The adipocyte differentiation caused to decrease the osteoclast formation-supporting activity, but did not affect osteoblastogenesis. The similar results were obtained from in vivo study. When human mesenchymal cells with BMP-2 and vitamin K2 inoculated to Matrigel and transplanted subcutaneously to nude mice, the cells was differentiated to osteoblasts and adipocytes by BMP-2. The effect of vitamin K2 on osteoblastogenesis failed to be observed in spite of the suppression of adipogenesis.These data indicate that the suppression of adipogenesis is not benefit for the protect of senescence-induced osteoporosis.