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

The Journal of Clinical Investigation
Chang-Jun LiXiang-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...Continue Reading

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Datasets Mentioned

BETA
GSE57127
GSE63725

Methods Mentioned

BETA
FACS
transfection
genotyping
chip
PCR
flow cytometry
bone marrow aspiration

Software Mentioned

FACS DIVE
TargetScan
Genespring
OsteoMeasureXP
PicTar
Partek Genomics Suite
miRanda
Feature Extraction

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