miR-23a/b regulates the balance between osteoblast and adipocyte differentiation in bone marrow mesenchymal stem cells

Abstract

Age-related osteoporosis is associated with the reduced capacity of bone marrow mesenchymal stem cells (BMSCs) to differentiate into osteoblasts instead of adipocytes. However, the molecular mechanisms that decide the fate of BMSCs remain unclear. In our study, microRNA-23a, and microRNA-23b (miR-23a/b) were found to be markedly downregulated in BMSCs of aged mice and humans. The overexpression of miR-23a/b in BMSCs promoted osteogenic differentiation, whereas the inhibition of miR-23a/b increased adipogenic differentiation. Transmembrane protein 64 (Tmem64), which has expression levels inversely related to those of miR-23a/b in aged and young mice, was identified as a major target of miR-23a/b during BMSC differentiation. In conclusion, our study suggests that miR-23a/b has a critical role in the regulation of mesenchymal lineage differentiation through the suppression of Tmem64.

Osteoporosis: Finding an age-related switch

Development of osteoporosis is linked to age-related decline in levels of two RNA molecules. Stem cells in the bone marrow (BMSCs) can turn into bone-generating cells (osteoblasts) or fat cells (adipocytes). In older individuals, the transition to adipocytes is more likely, leading to fatty bone marrow, bone loss, and osteoporosis. The molecular mechanisms underlying this age-related shift remained unclear. Zhangyuan Lin at the Xiangya Hospital of Central South University, China, and co-workers have identified two short, non-coding microRNAs, miR-23a and b, that regulate this shift. They found that bone marrow samples from young mice and humans contained higher levels of these microRNAs than those from older individuals. Using cultured mouse BMSCs, they confirmed that increasing or decreasing miR-23a and b correspondingly increased or decreased osteoblast formation. These results may facilitate development of novel therapies for osteoporosis.

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