Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression

Zhang,Long-Qiang; Zhao,Guang-Zong; Xu,Xiao-Yan; Fang,Jun; Chen,Jing-Ming; Li,Ji-Wen; Gao,Xue-Jian; Hao,Li-Juan; Chen,Yun-Zhen

doi:10.3892/ijmm.2015.2114

Integrin-β1 regulates chondrocyte proliferation and apoptosis through the upregulation of GIT1 expression

Authors:
- Long-Qiang Zhang
- Guang-Zong Zhao
- Xiao-Yan Xu
- Jun Fang
- Jing-Ming Chen
- Ji-Wen Li
- Xue-Jian Gao
- Li-Juan Hao
- Yun-Zhen Chen
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Affiliations: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Orthopedics, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China, Department of Oncology, Qingzhou Hospital of Traditional Chinese Medicine, Qingzhou, Shandong 262500, P.R. China, Department of Orthopedics, The 89th Hospital of PLA, Weifang, Shandong 261021, P.R. China, Department of Urologic Surgery, Yidu Central Hospital of Weifang, Weifang, Shandong 262500, P.R. China
Published online on: February 26, 2015 https://doi.org/10.3892/ijmm.2015.2114
Pages: 1074-1080

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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.

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