Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Klotho protects chondrocyte viability via FOXO1/3 in osteoarthritis

Wei Wei , Liefeng Ji, Wanli Duan, Jiang Zhu

Department of Orthopedics, Shaoxing Shangyu People's Hospital, Shaoxing, Zhejiang 312300, China;

For correspondence:- Wei Wei Email: 13967580259@163.com Tel:+8613967580259

Accepted: 1 September 2021 Published: 30 September 2021

Citation: Wei W, Ji L, Duan W, Zhu J. Klotho protects chondrocyte viability via FOXO1/3 in osteoarthritis. Trop J Pharm Res 2021; 20(9):1961-1968 doi: 10.4314/tjpr.v20i9.24

© 2021 The authors.
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Abstract

Purpose: To investigate the effect of Klotho and FOXO1/3 on the CH viability in OA.

Methods: The survival rate of CHs, Klotho and FOXO1/3 protein expression, and ROS production were measured in the OA cartilages of different degenerative phases. H₂O₂ was also used to injure CHs, and the cell viability, Klotho and FOXO1/3 expressions, as well as ROS levels were investigated to clarify the effect of exogenic Klotho on the injured CHs. Additionally, in order to verify the role of FOXO1/3 in Klotho-treated CHs, SOD2, GPX1, inflammatory factors, collagen I/II, SOX9, and Runx-2 levels were analyzed by silencing FOXO1 and FOXO3 expression via siRNA transfection.

Results: Klotho and FOXO1/3 expressions significantly decreased, and ROS production increased in severely human OA cartilage (p <0.05). Besides, H₂O₂ affected CHs viability with the suppression of Klotho and FOXO1/3 expression but ROS production was elevated. Exogenic Klotho application partly reversed the injury caused by H₂O₂. Furthermore, Klotho treatment of the injured CHs contributed to SOD2 and GPX1 expressions, and suppressed IL-1β, IL-6, TNF-α and MMP-13 production, resulting in the upregulation of collagen II and SOX9 as well as downregulation of collagen I and Runx-2. However, the protective effect of Klotho was weakened by FOXO1 and FOXO3 gene silencing.

Conclusion: Klotho protects CHs viability by suppressing oxidative stress and inflammation, which is associated with the mediation of FOXO1 and FOXO3. These findings provide new insights into the treatment of OA.

Keywords: Klotho, FOXO, Chondrocyte, Osteoarthritis, Oxidative stress