MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation

Chang Jun Li, Peng Cheng, Meng Ke Liang, Yu Si Chen, Qiong Lu, Jin Yu Wang, Zhu Ying Xia, Hou De Zhou, Xu Cao, Hui Xie, Er Yuan Liao, Xiang Hang Luo

Research output: Contribution to journalArticle

Abstract

Bone marrow mesenchymal stem cells (BMSCs) exhibit an age-dependent reduction in osteogenesis that is accompanied by an increased propensity toward adipocyte differentiation. This switch increases adipocyte numbers and decreases the number of osteoblasts, contributing to age-related bone loss. Here, we found that the level of microRNA-188 (miR-188) is markedly higher in BMSCs from aged compared with young mice and humans. Compared with control mice, animals lacking miR-188 showed a substantial reduction of age-associated bone loss and fat accumulation in bone marrow. Conversely, mice with transgenic overexpression of miR-188 in osterix+ osteoprogenitors had greater age-associated bone loss and fat accumulation in bone marrow relative to WT mice. Moreover, using an aptamer delivery system, we found that BMSC-specific overexpression of miR-188 in mice reduced bone formation and increased bone marrow fat accumulation. We identified histone deacetylase 9 (HDAC9) and RPTOR-independent companion of MTOR complex 2 (RICTOR) as the direct targets of miR-188. Notably, BMSC-specific inhibition of miR-188 by intra-bone marrow injection of aptamer-antagomiR-188 increased bone formation and decreased bone marrow fat accumulation in aged mice. Together, our results indicate that miR-188 is a key regulator of the age-related switch between osteogenesis and adipogenesis of BMSCs and may represent a potential therapeutic target for age-related bone loss.

Original languageEnglish (US)
Pages (from-to)1509-1522
Number of pages14
JournalJournal of Clinical Investigation
Volume125
Issue number4
DOIs
StatePublished - Apr 1 2015

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Li, C. J., Cheng, P., Liang, M. K., Chen, Y. S., Lu, Q., Wang, J. Y., Xia, Z. Y., Zhou, H. D., Cao, X., Xie, H., Liao, E. Y., & Luo, X. H. (2015). MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation. Journal of Clinical Investigation, 125(4), 1509-1522. https://doi.org/10.1172/JCI77716