The role of mir-124-3p in inhibiting osteogenic differentiation of bone marrow mesenchymal stem cell and reducing bone quality in senile osteoporosis

Abstract

Objective To investigate different expression levels between young and old bone marrow mesenchymal stem cells in microRNAs (miRNAs) that are significantly conserved between humans and mice. Additional studies have been conducted to discover changes in miRNA expression in old mice relative to that in young adults and discussed the roles of miRNAs in primary osteoporosis. Methods MiRNAs that are highly conserved between human and mice, and are expressed at significantly different levels in the bone marrow mesenchymal stem cells of young and old people were identified by searching the Gene Expression Omnibus (GEO) database. Human bone mesenchymal stem cells (hBMSCs) were transfected with miRNA mimics, and their relative alkaline phosphatase (ALP) activity levels were then determined. Micro-CT scanning was employed to quantitatively characterize cortical and cancellous bones of young and old mice, and to confirm that these mice accurately modeled natural aging osteoporosis. Simultaneously, we investigated differences in expression levels of miRNAs that influence ALP activity in hBMSCs in the two groups of mice. Correlations between miRNA expression levels, and parameters of bone mass and bone strength were studied. Results 28 miRNAs were found to be more than 2 fold up-regulated (down-regulated) with statistical significance (P<0.05) in the GEO database. We also found that ALP activity was lower in hBMSCs transfected with 4 miRNAs (mir-124-3p, mir-126-3p, mir-128-3p, mir-424-5p, P<0.05 or P<0.01). The micro-CT scans indicated that the mice are accurately modeled natural aging osteoporosis. Expression of mir-124-3p increased significantly in older mice. This upregulation correlated positively with trabecular separation, and negatively with trabecular pattern factor in trabecular bone. However, in cortical bone, its expression correlated positively with trabecular separation, and negatively with bone volume fraction, trabecular number, and bone mineral density (P<0.05). Conclusion Hsa-mir-124-3p, which is expressed differently in young and old bone marrow stromal cells, inhibited the osteogenic differentiation of hBMSCs. Upregulation of this miRNA in the bone tissue of aged mice may be related to the development of osteoporosis. Key words: Human bone marrow mesenchymal stem cells; mir-124-3p; Osteogenic differentiation