title: Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression.
abstract: Chondrocytes play a critical role in the repair process of osteoarthritis, which is also known as degenerative arthritis. Integrins, as the key family of cell surface receptors, are responsible for the regulation of chondrocyte proliferation, differentiation, survival and apoptosis through the recruitment and activation of downstream adaptor proteins. Moreover, G-protein-coupled receptor kinase interacting protein-1 (GIT1) exerts its effects on cell proliferation and migration through interaction with various cytokines. It has been previously suggested that GIT1 acts as a vital protein downstream of the integrin-mediated pathway. In the present study, we investigated the effects of integrin-β1 on cell proliferation and apoptosis, as well as the underlying mechanisms in chondrocytes in vitro. Following transfection with a vector expressing integrin-β1, our results revealed that the overexpression of integrin-β1 enhanced GIT1 expression, whereas the knockdown of integrin-β1 by siRNA suppressed GIT1 expression. However, no significant effect was observed on integrin-β1 expression following the enforced overexpression of GIT1, which suggests that GIT1 is localized downstream of integrin-β1. In other words, integrin-β1 regulates the expression of GIT1. Furthermore, this study demonstrated that integrin-β1 and GIT1 increased the expression levels of aggrecan and type II collagen, thus promoting chondrocyte proliferation; however, they inhibited chondrocyte apoptosis. Taken together, our data demonstrate that integrin-β1 plays a vital role in chondrocyte proliferation, differentiation and apoptosis. GIT1 exerts effects similar to those of integrin-β1 and is a downstream target of integrin-β1.
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Long-Qiang
authors.initials: LQ
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.
authors.forename: Guang-Zong
authors.initials: GZ
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Qingzhou Hospital of Traditional Chinese Medicine, Qingzhou, Shandong 262500, P.R. China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Fang
authors.affiliation: Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.
authors.forename: Jing-Ming
authors.initials: JM
authors.lastname: Chen
authors.affiliation: Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.
authors.forename: Ji-Wen
authors.initials: JW
authors.lastname: Li
authors.affiliation: Department of Orthopedics, The 89th Hospital of PLA, Weifang, Shandong 261021, P.R. China.
authors.forename: Xue-Jian
authors.initials: XJ
authors.lastname: Gao
authors.affiliation: Department of Urologic Surgery, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China.
authors.forename: Li-Juan
authors.initials: LJ
authors.lastname: Hao
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Yun-Zhen
authors.initials: YZ
authors.lastname: Chen
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D049109:Cell Proliferation; D019902:Chondrocytes / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D019012:Integrin beta1 / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics*; D051381:Rats
chemical_list: D018797:Cell Cycle Proteins; C485648:Git1 protein, rat; D019012:Integrin beta1; D010750:Phosphoproteins