Selonsertib Alleviates the Progression of Rat Osteoarthritis: An in vitro and in vivo Study.

Jiyuan Yan,Yifan Xiao,Huaixi Wang,Shanxi Wang,Bowei Ni,Yingchi Zhang,Hua Wu,Yongzhuang Ma,Tianqi Wang,Gaohong Sheng,Chang Tu

doi:10.3389/fphar.2021.687033

Abstract

Osteoarthritis (OA) is a prevalent degenerative joint disease. Its development is highly associated with inflammatory response and apoptosis in chondrocytes. Selonsertib (Ser), the inhibitor of Apoptosis Signal-regulated kinase-1 (ASK1), has exhibited multiple therapeutic effects in several diseases. However, the exact role of Ser in OA remains unclear. Herein, we investigated the anti-arthritic effects as well as the potential mechanism of Ser on rat OA. Our results showed that Ser could markedly prevent the IL-1β-induced inflammatory reaction, cartilage degradation and cell apoptosis in rat chondrocytes. Meanwhile, the ASK1/P38/JNK and NFκB pathways were involved in the protective roles of Ser. Furthermore, intra-articular injection of Ser could significantly alleviate the surgery induced cartilage damage in rat OA model. In conclusion, our work provided insights into the therapeutic potential of Ser in OA, indicating that Ser might serve as a new avenue in OA treatment.

Highlights

Osteoarthritis (OA), featured with joint pain, stiffness and dysfunction, is the most frequently seen degenerative arthritis in the elderly (Glyn-Jones et al, 2015)
The cytotoxic effects of different doses of Ser with or without IL1β (10 ng/ml) on cultured rat chondrocytes were determined via Cell Counting Kit-8 (CCK-8) assay
We investigated the exact role of Ser on IL-1β-induced Apoptosis Signal-regulated kinase-1 (ASK1)/P38/ JNK pathway activation in cultured chondrocytes

Summary

Introduction

Osteoarthritis (OA), featured with joint pain, stiffness and dysfunction, is the most frequently seen degenerative arthritis in the elderly (Glyn-Jones et al, 2015). The prevalence of OA continues to rise globally. It is the leading cause of chronic pain and impaired physical mobility in aged population (Losina et al, 2013; Saberi Hosnijeh et al, 2019). Joint replacement surgery is the only choice for patients in end-stage OA (Bellamy et al, 2006). This undoubtedly brings huge burden to the society and individuals

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