4.4 Article

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

Journal

MOLECULAR BIOLOGY OF THE CELL
Volume 22, Issue 21, Pages 3955-3961

Publisher

AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E11-04-0356

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Funding

  1. Li Ka Shing Institute of Health Sciences
  2. Chinese University of Hong Kong and Science & Technology Office of Hei-Longjiang Province [PG09J003]

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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.

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