BMSCs-derived exosomal miR-196a-5p promotes macrophage M2 polarization and osteogenesis in postmenopausal osteoporosis through regulating Rspo2/Wnt/β-catenin signaling.

This study aimed to investigate the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-EXOs) on postmenopausal osteoporosis (PMOP). Bilateral ovariectomy (OVX) surgery was performed to establish mouse PMOP models. Histological analysis was conducted using hematoxylin and eosin staining. Gene expression was detected using immunohistochemistry and Western blot. miRNA and mRNA were detected using quantitative reverse transcriptase PCR. Cell functions were analyzed using oil red O, alizarin red, and alkaline phosphatase (ALP) staining, and flow cytometry. The interaction between miR-196a-5p and R-spondin 2 (Rspo2) was verified by luciferase and RNA immunoprecipitation assays. We found that BMSCs-EXOs promoted osteogenesis and macrophage M2 polarization. BMSCs-derived exosomal miR-196a-5p enhanced the effects of BMSCs-EXOs on mediating osteogenesis and M2 polarization. Mechanistically, miR-196a-5p targeted Rspo2, activating Wnt/β-Catenin signaling. BMSCs-derived exosomal miR-196a-5p alleviated the effects of M1 macrophages and promoted the osteogenesis of BMSCs, which was reversed by Rspo2. Furthermore, BMSCs-derived exosomal miR-196a-5p promoted the osteogenesis in vivo. However, miR-196a-5p inhibitor exerted the opposite effects, which was reversed by recombinant IL-10. Taken together, BMSCs-derived exosomal miR-196a-5p protects against PMOP by driving macrophage M2 polarization though regulating Rspo2/Wnt/β-Catenin signaling. Therefore, targeting cell-cell communication in the microenvironment of bone lesions may be a promising strategy for PMOP.