TRAF3, a Target of MicroRNA-363-3p, Suppresses Senescence and Regulates the Balance Between Osteoblastic and Adipocytic Differentiation of Rat Bone Marrow-Derived Mesenchymal Stem Cells

Abstract

Bone marrow-derived mesenchymal stem cells (BMSCs) have the potential to differentiate into osteoblasts or adipocytes, and an imbalance between adipogenesis and osteogenesis causes age-related bone loss. In this study, we determined the influence of tumor necrosis factor receptor-associated factor 3 (TRAF3) on senescence and osteoblastic and adipocytic differentiation of rat BMSCs. TRAF3 expression increased during osteogenic differentiation but decreased during adipocytic differentiation of rat BMSCs, and compared with day 0 cultures, on day 14, the differences were significant. Overexpression of TRAF3 significantly promoted BMSC osteogenic differentiation and suppressed adipogenic differentiation and senescence. Furthermore, Traf3 was determined to be a target gene of miR-363-3p in BMSCs, and TRAF3 expression in BMSCs was reduced by miR-363-3p overexpression. This overexpression attenuated the effects of TRAF3 on BMSC adipogenic differentiation, osteogenic differentiation, and senescence. Taken together, these results uncovered the mechanism by which TRAF3 promotes BMSC osteogenic differentiation and suppresses adipogenic differentiation and senescence, indicating that the miR-363-3p-TRAF3 axis might be a novel therapeutic target for BMSC-based bone tissue engineering in osteoporosis.

Keywords: TRAF3; adipogenic differentiation; bone marrow-derived mesenchymal stem cells; miR-363-3p; osteogenic differentiation; senescence.