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.
Highlights
Type 1 diabetes mellitus is an increasingly prevalent systemic disease in the world
We investigated the influence and underlying mechanisms of rhPDGF-BB involved in the regulation of proliferation and osteogenesis of Bone marrow stromal cells (BMSCs) derived from diabetic rats
To determine how rhPDGF-BB promoted the functions of diabetic BMSCs, we investigated whether extracellular signal regulated kinase (ERK) pathway in diabetic BMSCs was activated by rhPDGF-BB treatment
Summary
Type 1 diabetes mellitus is an increasingly prevalent systemic disease in the world. In 2012, the prevalence of diabetes was estimated to be 8.3% worldwide, representing approximately 371 million people living with diabetes [1]. BMSCs are obtained and expanded in vitro, and they are self-renewing, multipotent stem cells that have the capability of differentiating into osteoblasts, chondrocytes, adipocytes, tenocytes, and myoblasts As their easy availability and multipotent potential, BMSCs are demonstrated as an attractive candidate for tissue engineering applications, which has been effectively used to enhance bone repair and regeneration [13]. Increased proliferation and osteoblast differentiation in many types of cells induced by rhPDGF-BB have been widely reported previously, little information is available about its effect on diabetic BMSCs. In this study, we investigated the influence and underlying mechanisms of rhPDGF-BB involved in the regulation of proliferation and osteogenesis of BMSCs derived from diabetic rats. This information may shed light on the effect of rhPDGF-BB on bone metabolism and its mechanism in counteracting bone disorders in diabetes
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