RhPDGF-BB promotes proliferation and osteogenic differentiation of bone marrow stromal cells from streptozotocin-induced diabetic rats through ERK pathway

Abstract

Management of nonunion fracture and massive segmental bone defects in diabetes remains a challenging clinical problem. Bone marrow stromal cells (BMSCs) are crucial for bone remodeling and hold promise for bone regeneration. However, we have showed previously that diabetes can affect the proliferation and osteogenic potential of BMSCs adversely and a strategy to attenuate the impaired functions of BMSCs is required. Platelet-derived growth factor-BB (PDGF-BB) plays an important role in bone formation. However, little information is available about its effect on diabetic BMSCs. In this study, BMSCs were isolated from streptozotocin-induced diabetic rats. After treatment with recombinant human PDGF-BB (rhPDGF-BB), diabetic BMSCs demonstrated enhanced cell proliferation and osteogenic differentiation based on increased expressions of osteogenic genes (Runx2, alkaline phosphatase, and osteocalcin) and Runx2 protein, as well as upregulated alkaline phosphatase activity and mineralization. Furthermore, blocking extracellular signal regulated kinase (ERK) pathway by inhibitor PD98059 repressed the enhanced proliferation and osteogenic differentiation in diabetic BMSCs induced by rhPDGF-BB. Together, these results indicated that rhPDGF-BB stimulates proliferation and osteogenic differentiation partially through ERK pathway in diabetic BMSCs. Therefore, modulation of diabetic BMSCs could augment BMSCs function affected by diabetes and holds significance for future strategies to treat diabetic bone complications. © 2014 Yanfang Zhao et al.