We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
MicroRNA-188 regulates age-related switch between osteoblast and adipocyte differentiation.
- Authors
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
- 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.
- Subjects
MICRORNA; OSTEOBLASTS; FAT cells; MESENCHYMAL stem cells; BONE marrow; ADIPOGENESIS; BONE growth; LABORATORY mice
- Publication
Journal of Clinical Investigation, 2015, Vol 125, Issue 4, p1509
- ISSN
0021-9738
- Publication type
Article
- DOI
10.1172/JCI77716