Exosomal miR-186 Derived from BMSCs Promote Osteogenesis Through Hippo Signaling Pathway in Postmenopausal Osteoporosis

Abstract

Background: Postmenopausal osteoporosis (PMO) that results from estrogen withdrawal is the most common primary osteoporosis among older women. However, little is known about the mechanism of PMO, and effective treatment of PMO is limited.Methods: We used qPCR, western blotting, and RNA pull down to investigate the relationship between miR-186 and Mob1. Also we investigated the effect of exosome in osteogenesis using ALP staining. And HE staining was used to verify the osteogenesis in PMO model.Results: Exosomal miR-186 plays an important role in bone formation. The results of miRNA-seq and q-PCR showed that miR-186 was upregulated in a PMO+Exo treatment group. Results of RNA-pull down and luciferase reporter assays verified interactions between miR-186 and Mob1. We also verified the Hippo signaling pathway plays an important role in osteogenesis.Conclusions: We concluded that exosomes derived from hBMSCs can transfer miR-186 to promote osteogenesis in ovariectomy (OVX) rats through the Hippo signaling pathway.

Role of Exosomal MicroRNAs and Their Crosstalk with Oxidative Stress in the Pathogenesis of Osteoporosis

“…These special features allow exos to play a regulatory role in certain diseases. The functional effects of exosomal miRNAs in OP have been well documented (Table 1) [52,[78][79][80][81]. Li et al reported that exos derived from MSCs can effectively ameliorate the development of OP, and exosomal miR-186 participates in this regulatory process [81].…”

“…The functional effects of exosomal miRNAs in OP have been well documented (Table 1) [52,[78][79][80][81]. Li et al reported that exos derived from MSCs can effectively ameliorate the development of OP, and exosomal miR-186 participates in this regulatory process [81]. Moreover, a recent study demonstrated that exosomal miR-1263 derived from human umbilical cord MSCs can inhibit osteoblast apoptosis and that nanomaterials loaded with miR-1263 may be ideal alternatives for the treatment of bone resorption disorders [80].…”