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miR-637 通过直接靶向 Osterix 来维持脂肪细胞和成骨细胞之间的平衡。

MiR-637 maintains the balance between adipocytes and osteoblasts by directly targeting Osterix.

机构信息

Stanley Ho Centre for Emerging Infectious Diseases, Third Military Medical University, Chongqing, 400038, PR China.

出版信息

Mol Biol Cell. 2011 Nov;22(21):3955-61. doi: 10.1091/mbc.E11-04-0356. Epub 2011 Aug 31.

Abstract

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.

摘要

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。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f371/3204058/2b9cc8dead0d/3955fig1.jpg

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