Fibulin-5 protects the extracellular matrix of chondrocytes by inhibiting the Wnt/β-catenin signaling pathway and relieves osteoarthritis

J.-B. Gao, L. Lin, X.-Q. Men, J.-B. Zhao, M.-H. Zhang, L.-P. Jin, S.-J. Gao, S.-Q. Zhao, J.-T. Dong

Department of Hand and Foot Surgery, Third Hospital of Shijiazhuang, Shijiazhuang, China. djtloveyz@outlook.com

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• Orthopedics

OBJECTIVE: Osteoarthritis (OA) is a common disease in the elderly and seriously affects the quality of life of patients. The purpose of this study was to explore the protective effect of Fibulin-5 on articular chondrocytes and its mechanism of action.

PATIENTS AND METHODS: Articular cartilage tissues from patients with OA and normal people were selected and tested for differences in Fibulin-5 expression. In addition, human chondrocytes were cultured, and the effects of Fibulin-5 on the extracellular matrix (ECM) of chondrocytes and the level of inflammation were examined by means of cell transfection and cytokine intervention. SKL2001, an agonist of the Wnt/β-catenin signaling pathway, was used to validate the mechanism of action of Fibulin-5 to protect chondrocytes.

RESULTS: Fibulin-5 was lowly expressed in the cartilage tissue of patients with OA. Overexpression of Fibulin-5 significantly increased the expressions of ECM collagen II and aggrecan in chondrocytes, while decreasing the expressions of MMP-3 and MMP-13. In addition, Fibulin-5 reduced IL-1β-induced inflammation of chondrocytes, as well as expressions of IL-6, IL-8, and TNF-α. Overexpression of Fibulin-5 also reduced the activity of Wnt/β-catenin signaling pathway, and activation of Wnt/β-catenin signaling pathway attenuated the protective effects of Fibulin-5 on the ECM of chondrocytes.

CONCLUSIONS: Fibulin-5 can protect the ECM of chondrocytes and reduce the inflammatory response of chondrocytes by inhibiting the Wnt/β-catenin signaling pathway.

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