Mmu-miR-185 depletion promotes osteogenic differentiation and suppresses bone loss in osteoporosis through the Bgn-mediated BMP/Smad pathway

Abstract

MicroRNAs (miRs) play an essential role in the regulation of bone formation and homeostasis. miR-185 has been reported to negatively regulate osteogenesis in vitro. However, whether it has an impact on in vivo bone homeostasis remains unknown. Here, we demonstrated that primary osteoblasts and mesenchymal stem cells derived from miR-185-knockout (KO) mice exhibited enhanced osteogenesis. Further, we constructed an ovariectomized mouse model to investigate the role of miR-185 during osteoporosis. Micro-computed tomography revealed an increased bone volume in KO compared to wild-type mice 6 weeks after surgery, indicating redundant bone formation after miR-185 depletion. Dual-luciferase reporter assays identified biglycan (Bgn), which promotes bone formation through the BMP/Smad pathway, as the direct target of miR-185. Taken together, these findings indicate that blocking miR-185 expression increases bone formation during osteoporosis, which may partly occur through the regulation of Bgn expression and BMP/Smad signaling.

Circular RNA SIPA1L1 promotes osteogenesis via regulating the miR-617/Smad3 axis in dental pulp stem cells

“…Dysfunctional miRNAs in osteoporosis have been proven to exert a certain therapeutic potential. Bone destruction and strength are greatly improved in osteoporosis mice intravenously administrated with chemically synthesized miR-106b-5p, miR-17-5p, or miR-451 [24].…”

The Effect of miR122 and miR185 on Hepatic Differentiation of Human Umbilical Cord Mesenchymal Stem Cells

“…It has been shown that overexpression of miR185 can lead to a signi cant reduction in lipid accumulation, while the low level of miR185 can promote adipogenic differentiation [32] . Studies have demonstrated that the inhibition of miR185 could promote bone formation and osteogenic differentiation [33,42,43] . In this study, it was found that the expressions of hepatic relative genes and proteins by cells overexpression of miR185 induction group were decreased compared with normal hUC-MSCs after hepatic induction differentiation, which means, differentiation of hUC-MSCs was delayed by overexpression of miR185.…”

miR‑205 regulates bone turnover in elderly female patients with type 2 diabetes mellitus through targeted inhibition of Runx2

“…Microribonucleic acids (microRNAs or miRs) are a type of single-stranded, non-coding and small-molecule RNAs approximately 18-25 nucleotides in length, which are involved in the occurrence and progression of various diseases ( 7 , 8 ). It has been reported that some miRs can participate in bone turnover, bone metabolism and bone development, thereby regulating the occurrence and progression of OP ( 9-11 ). However, whether there is a certain association between miRs and T2DM + OP has not yet been reported.…”