title: Stem cell factor (SCF) protects osteoblasts from oxidative stress through activating c-Kit-Akt signaling.
abstract: Osteoblasts regulate bone formation and remodeling, and are main target cells of oxidative stress in the progression of osteonecrosis. The stem cell factor (SCF)-c-Kit pathway plays important roles in the proliferation, differentiation and survival in a range of cell types, but little is known about its functions in osteoblasts. In this study, we found that c-Kit is functionally expressed in both osteoblastic-like MC3T3-E1 cells and primary murine osteoblasts. Its ligand SCF exerted significant cyto-protective effects against hydrogen peroxide (H₂O₂). SCF activated its receptor c-Kit in osteoblasts, which was required for its cyto-protective effects against H₂O₂. Pharmacological inhibition (by Imatinib and Dasatinib) or shRNA-mediated knockdown of c-Kit thus inhibited SCF-mediated osteoblast protection. Further investigations showed that protection by SCF against H₂O₂ was mediated via activation of c-Kit-dependent Akt pathway. Inhibition of Akt activation, through pharmacological or genetic means, suppressed SCF-mediated anti-H₂O₂ activity in osteoblasts. In summary, we have identified a new SCF-c-Kit-Akt physiologic pathway that protects osteoblasts from H₂O₂-induced damages, and might minimize the risk of osteonecrosis caused by oxidative stress.
authors.affiliation: Department of Orthopedics, Changzhou Wujin People's Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, Changzhou Wujin People's Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Yin
authors.affiliation: Department of Orthopedics, Changzhou Wujin People's Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Orthopedics, Changzhou Wujin People's Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Guan
authors.affiliation: Department of Orthopedics, Changzhou Wujin People's Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou, China.
authors.forename: Xiaoqiang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: jianguangwang@163.com.
authors.forename: Jianguang
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Changzhou Wujin People's Hospital-South Division, Affiliated Hospital of Jiangsu University, Changzhou, China. Electronic address: gehujianguo68@163.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Zhu
mesh_terms: D016475:3T3 Cells; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival; D004797:Enzyme-Linked Immunosorbent Assay; D006861:Hydrogen Peroxide / Q000737:chemistry; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008024:Ligands; D051379:Mice; D009336:Necrosis / Q000473:pathology; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism*
chemical_list: D008024:Ligands; D019089:Stem Cell Factor; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D019009:Proto-Oncogene Proteins c-kit; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: Akt; Osteoblasts; Oxidative stress; Stem cell factor; c-Kit