Abstract
As the population ages, the medical and socioeconomic impact of age-related bone disorders will further increase. An imbalance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) can lead to various bone and metabolic diseases such as osteoporosis. Thus, understanding the molecular mechanisms underlying MSC osteogenic and adipogenic differentiation is important for the discovery of novel therapeutic paradigms for these diseases. miR-10b has been widely reported in tumorigenesis, cancer invasion and metastasis. However, the effects and potential mechanisms of miR-10b in the regulation of MSC adipogenic and osteogenic differentiation have not been explored. In this study, we found that the expression of miR-10b was positively correlated with bone formation marker genes ALP, RUNX2 and OPN, and negatively correlated with adipogenic markers CEBPα, PPARγ and AP2 in clinical osteoporosis samples. Overexpression of miR-10b enhanced osteogenic differentiation and inhibited adipogenic differentiation of human adipose-derived mesenchymal stem cells (hADSCs) in vitro, whereas downregulation of miR-10b reversed these effects. Furthermore, miR-10b promoted ectopic bone formation in vivo. Target prediction and dual luciferase reporter assays identified SMAD2 as a potential target of miR-10b. Silencing endogenous SMAD2 expression in hADSCs enhanced osteogenesis but repressed adipogenesis. Pathway analysis indicated that miR-10b promotes osteogenic differentiation and bone formation via the TGF-β signaling pathway, while suppressing adipogenic differentiation may be primarily mediated by other pathways. Taken together, our findings imply that miR-10b acts as a critical regulator for balancing osteogenic and adipogenic differentiation of hADSCs by repressing SMAD2 and partly through the TGF-β pathway. Our study suggests that miR-10b is a novel target for controlling bone and metabolic diseases.
Highlights
As the population ages, the medical and socioeconomic impact of age-related bone disorders will further increase
According to fold change and P-values, we found that the expression of miR-10b regulates osteogenesis and adipogenesis miR-10b increased during osteogenic differentiation but decreased during adipogenic differentiation
The results showed that miR-10b increased during osteogenic differentiation but decreased during adipogenic differentiation (Fig. 1A), suggesting that miR10b is involved in regulating the balance of adipogenesis and osteogenesis of human adipose-derived mesenchymal stem cells (hADSCs)
Summary
The medical and socioeconomic impact of age-related bone disorders will further increase. An imbalance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) can lead to various bone and metabolic diseases such as osteoporosis. A clear understanding of the molecular mechanisms governing the balance between osteogenic and adipogenic differentiation of MSCs is of great significance to elucidate the pathogenesis of bone and metabolic diseases, and to develop novel and effective therapies. Only a few miRNAs have been implicated to be responsible for both processes, such as miR-204 [24], miR-17-5p, miR-106a [25], miR-30e [26] and miR-194 [27] It suggests that adipocyte and osteoblast differentiation are tightly regulated by specific miRNAs in hMSCs. miR-10b is a well-known oncogenic miRNA and can promote growth and metastasis of cancer cells. The effects and potential mechanisms of miR-10b in the regulation of MSC adipogenic and osteogenic differentiation have not been explored
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