title: Tumor necrosis factor alpha suppresses osteogenic differentiation of MSCs by inhibiting semaphorin 3B via Wnt/β-catenin signaling in estrogen-deficiency induced osteoporosis.
abstract: The proinflammatory cytokines, especially tumor necrosis factor alpha (TNF-α), 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-α 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-α, suppressing Semaphorin3B expression contributes to estrogen-deficiency-induced osteoporosis. In this study, we found that TNF-α could decrease Semaphorin3B expression in osteogenic differentiation of MSCs. Overexpression of Semaphorin3B in MSCs attenuated the inhibitory effects of TNF-α on MSCs proliferation and osteoblastic differentiation. Mechanistically, activation of the Wnt/β-catenin signaling markedly rescued TNF-α-inhibited Semaphorin3B expression, suggesting that Wnt/β-catenin signaling was involved in the regulation of Semaphorin3B expression by TNF-α. Taken together, our results revealed a novel function for Semaphorin3B and suggested that suppressed Semaphorin3B may contribute to impaired bone formation by elevated TNF-α in estrogen-deficiency-induced osteoporosis. This study may indicate a therapeutic target gene of Semaphorin3B for osteoporosis.
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Department of Orthopaedics, Second Military Medical University's Jinan Clinical Medicine College, Jinan, China; Department of Orthaopedics, General Hospital of Jinan Military Command, Jinan 250031, Shandong, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Sang
authors.affiliation: Department of Orthopaedics, Second Military Medical University's Jinan Clinical Medicine College, Jinan, China; Department of Orthaopedics, General Hospital of Jinan Military Command, Jinan 250031, Shandong, China.
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Orthopaedics, Second Military Medical University's Jinan Clinical Medicine College, Jinan, China; Department of Orthaopedics, General Hospital of Jinan Military Command, Jinan 250031, Shandong, China.
authors.forename: Fangjing
authors.initials: F
authors.lastname: Chen
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Huang
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Qi
authors.affiliation: Department of Orthopaedics, Second Military Medical University's Jinan Clinical Medicine College, Jinan, China; Department of Orthaopedics, General Hospital of Jinan Military Command, Jinan 250031, Shandong, China.
authors.forename: Pingshan
authors.initials: P
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Orthopaedics, Second Military Medical University's Jinan Clinical Medicine College, Jinan, China; Department of Orthaopedics, General Hospital of Jinan Military Command, Jinan 250031, Shandong, China. Electronic address: caoxuecheng_sm@126.com.
authors.forename: Xuecheng
authors.initials: X
authors.lastname: Cao
authors.affiliation: Shanghai Key Laboratory for Bone and Joint Diseases, Shanghai Institute of Orthopaedics and Traumatology, Shanghai Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. Electronic address: guolei607@126.com.
authors.forename: Lei
authors.initials: L
authors.lastname: Guo
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D004967:Estrogens / Q000172:deficiency*; D005260:Female; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D008810:Mice, Inbred C57BL; D010012:Osteogenesis; D010024:Osteoporosis / Q000209:etiology* / Q000378:metabolism; D010052:Ovariectomy; D039961:Semaphorins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D004967:Estrogens; D039961:Semaphorins; D014409:Tumor Necrosis Factor-alpha
keywords: MSCs; Osteogenesis; Semaphorin3B; TNF-α, Wnt/β-catenin signaling