Stanley Ho Centre for Emerging Infectious Diseases, Third Military Medical University, Chongqing, 400038, PR China.
Mol Biol Cell. 2011 Nov;22(21):3955-61. doi: 10.1091/mbc.E11-04-0356. Epub 2011 Aug 31.
Bone development is dynamically regulated by homeostasis, in which a balance between adipocytes and osteoblasts is maintained. Disruption of this differentiation balance leads to various bone-related metabolic diseases, including osteoporosis. In the present study, a primate-specific microRNA (miR-637) was found to be involved in the differentiation of human mesenchymal stem cells (hMSCs). Our preliminary data indicated that miR-637 suppressed the growth of hMSCs and induced S-phase arrest. Expression of miR-637 was increased during adipocyte differentiation (AD), whereas it was decreased during osteoblast differentiation (OS), which suggests miR-637 could act as a mediator of adipoosteogenic differentiation. Osterix (Osx), a significant transcription factor of osteoblasts, was shown to be a direct target of miR-637, which significantly enhanced AD and suppressed OS in hMSCs through direct suppression of Osx expression. Furthermore, miR-637 also significantly enhanced de novo adipogenesis in nude mice. In conclusion, our data indicated that the expression of miR-637 was indispensable for maintaining the balance of adipocytes and osteoblasts. Disruption of miR-637 expression patterns leads to irreversible damage to the balance of differentiation in bone marrow.
骨骼发育是通过维持脂肪细胞和成骨细胞之间的平衡来动态调节的。这种分化平衡的破坏会导致各种与骨骼相关的代谢疾病，包括骨质疏松症。在本研究中，发现一种灵长类动物特异性 microRNA（miR-637）参与了人间充质干细胞（hMSC）的分化。我们的初步数据表明，miR-637 抑制 hMSC 的生长并诱导 S 期停滞。miR-637 的表达在脂肪细胞分化（AD）期间增加，而在成骨细胞分化（OS）期间减少，这表明 miR-637 可以作为脂肪成骨分化的介质。成骨细胞的重要转录因子 Osterix（Osx）被证明是 miR-637 的直接靶标，通过直接抑制 Osx 的表达，miR-637 显著增强了 hMSC 中的 AD，并抑制了 OS。此外，miR-637 还显著增强了裸鼠中的新生脂肪生成。总之，我们的数据表明，miR-637 的表达对于维持脂肪细胞和成骨细胞之间的平衡是必不可少的。miR-637 表达模式的破坏会导致骨髓分化平衡的不可逆损害。
