Exosomal miR-29a Derived from Bone Marrow Mesenchymal Stem Cells Promotes Mouse Bone Development and Formation

Abstract

Bone undergoes constant remodeling during development, and the maintenance of its function requires a dynamic balance between bone formation and resorption by osteoclasts. With unique bone resorption capabilities, as large multinucleated cells, osteocytes participate in bone remodeling and they are produced by the mononuclear/macrophage cells under activation of Wnt and Runx2. The mechanism underlying osteogenesis remains unclear. We investigated the impact of exosomal miR-29a derived from BMSCs on bone development and formation. In this study, BMSCs were transfected and then injected into mice followed by analysis of femur and skull development and regeneration by HE staining and CT scanning, and the expression of DKK1, Runx-2, and osteogenic biomarkers (Osterix, Satb2, ALP, and BSP) by western blot and RT-qPCR. Compared with mice in miR-29a inhibitor group, the femur and skull of mice in miRNA NC group were more complete. miR-29a derived from BMSCs induced a decrease of DKK1 expression and increase of the expression of β-catenin and osteogenic transcription factors. In conclusion, this study demonstrates that BMSC-derived exosomes miR-29a facilitates osteogenesis in mice through inhibition of DKK1 expression.