Tumor necrosis factor alpha suppresses osteogenic differentiation of MSCs by inhibiting semaphorin 3B via Wnt/β-catenin signaling in estrogen-deficiency induced osteoporosis

The proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-alpha), have been shown to inhibit osteogenic differentiation of mesenchymal stem cells (MSCs) and bone formation in estrogen-deficiency-induced osteoporosis, but the mechanisms of TNF-alpha impaired bone formation remain poorly understood. Semaphorins have been shown to regulate cell growth, cell migration, and cell differentiation in a variety of tissues, including bone tissue. Here, we identified a novel mechanism whereby TNF-alpha, suppressing Semaphorin3B expression contributes to estrogen-deficiency-induced osteoporosis. In this study, we found that TNF-alpha could decrease Semaphorin3B expression in osteogenic differentiation of MSCs. Overexpression of Semaphorin3B in MSCs attenuated the inhibitory effects of TNF-alpha. on MSCs proliferation and osteoblastic differentiation. Mechanistically, activation of the Wnt/beta-catenin signaling markedly rescued TNF-alpha-inhibited Semaphorin3B expression, suggesting that Wnt/beta-catenin signaling was involved in the regulation of Semaphorin3B expression by TNF-alpha. Taken together, our results revealed a novel function for Semaphorin3B and suggested that suppressed Semaphorin3B may contribute to impaired bone formation by elevated TNF-alpha in estrogen-deficiency-induced osteoporosis. This study may indicate a therapeutic target gene of Semaphorin3B for osteoporosis. (C) 2015 Elsevier Inc. All rights reserved.