Xiaoyong Chen1, Yuewei Li2, Minghui Zhang2, Xiaoqing Wu1, Jinyu Zhu1. 1. Department of Joint and Trauma, Shenzhen University General Hospital, Shenzhen, P.R. China. 2. Department of Orthopaedics, Xiamen 174 Hospital, Xiamen, P.R. China.
Abstract
BACKGROUND: Osteoarthritis (OA) represents a significant disabling condition that has been well documented as a significant health burden. Lymphocyte-specific kinase (LCK) has been reported to exhibit differential expression in OA. However, the specific mechanism of LCK in OA remains relatively unknown. Herein, the current study aimed to elucidate the role of LCK in cartilage injury in OA in relation to the nuclear factor-kappa B (NF-κB) pathway. METHODS: The expression of LCK was determined in the collected cartilage tissues of patients with OA as well as the OA rat models. Gain- and loss-of-function approaches were conducted on the OA rat model as well as the interleukin-1β (IL-1β)-induced in vitro OA model to further explore the role of LCK in chondrocyte proliferation and apoptosis, extracellular matrix (ECM) degradation and inflammation. RESULTS: LCK was highly expressed in the cartilage tissues of both patients and rats with OA. LCK silencing led to a reduction in the rate of apoptosis, inflammation, and degree of ECM degradation in the cartilage tissues of OA rats. In the IL-1β-induced chondrocytes, LCK silencing repressed apoptosis, inflammation and ECM degradation, while acting to elevate viability. LCK silencing inhibited activation of NF-κB in OA. LCK was found to activate the NF-κB pathway which heightened apoptosis, inflammation and ECM degradation while lowering viability in the IL-1β-induced chondrocytes. CONCLUSION: Taken together, our study demonstrates that silencing of LCK promotes cartilage repair in OA by inhibiting the NF-κB pathway and diminishing IL-1β-induced chondrocyte inflammation as well as ECM degradation. This article is protected by copyright. All rights reserved.
BACKGROUND:Osteoarthritis (OA) represents a significant disabling condition that has been well documented as a significant health burden. Lymphocyte-specific kinase (LCK) has been reported to exhibit differential expression in OA. However, the specific mechanism of LCK in OA remains relatively unknown. Herein, the current study aimed to elucidate the role of LCK in cartilage injury in OA in relation to the nuclear factor-kappa B (NF-κB) pathway. METHODS: The expression of LCK was determined in the collected cartilage tissues of patients with OA as well as the OA rat models. Gain- and loss-of-function approaches were conducted on the OA rat model as well as the interleukin-1β (IL-1β)-induced in vitro OA model to further explore the role of LCK in chondrocyte proliferation and apoptosis, extracellular matrix (ECM) degradation and inflammation. RESULTS:LCK was highly expressed in the cartilage tissues of both patients and rats with OA. LCK silencing led to a reduction in the rate of apoptosis, inflammation, and degree of ECM degradation in the cartilage tissues of OA rats. In the IL-1β-induced chondrocytes, LCK silencing repressed apoptosis, inflammation and ECM degradation, while acting to elevate viability. LCK silencing inhibited activation of NF-κB in OA. LCK was found to activate the NF-κB pathway which heightened apoptosis, inflammation and ECM degradation while lowering viability in the IL-1β-induced chondrocytes. CONCLUSION: Taken together, our study demonstrates that silencing of LCK promotes cartilage repair in OA by inhibiting the NF-κB pathway and diminishing IL-1β-induced chondrocyte inflammation as well as ECM degradation. This article is protected by copyright. All rights reserved.