Bone Marrow Stromal Cells Promote Osteogenic Differentiation and Induce Bone Remodeling and Healing in Osteoporosis.

Abstract

OBJECTIVE: Osteoporosis is a common disorder marked by bone loss, fragility, and fractures. microRNAs (miRNAs) are highlighted as potential regulators of osteoblast differentiation, and exosomes carrying miRNAs from bone marrow stromal cells (BMSCs) are applied to treatment. Herein, we aimed to clarify the role of miR-17 and BMSCs in ovariectomized rats with osteoporosis. METHODS: After establishment of an osteoporosis animal model, miR-17 and BARX2 expression in ovariectomized rat tissues and osteoblasts were detected. Osteoblasts were transfected with mimics and inhibitor and co-cultured with BMSCs, whilst cell proliferation and differentiation were evaluated. RESULTS: miR-17 was poorly expressed in ovariectomized rat tissue, while BARX2 was up-regulated. Overexpression of miR-17 induced decreased BARX2 expression but enhanced proliferation and differentiation of osteoblasts in osteoporotic rats. Importantly, the presence of BMSCs also facilitated osteoblast differentiation and decreased BARX2 expression, which was abolished by addition of exosome inhibitors. Mechanistically, miR-17 targeted BARX2 expression to up-regulate ALP and Co1-I in osteoporosis. CONCLUSION: Collectively, miR-17 delivered by BMSC exosomes promotes osteogenic differentiation and induces bone healing in osteoporosis through BARX2 regulation. The combined use of exosome inhibitors confirmed the therapeutic effect of BMSCs and BMSC exosomes containing miRNAs on various diseases.