SOCS1 Regulates Apoptosis and Inflammation by Inhibiting IL-4 Signaling in IL-1β-Stimulated Human Osteoarthritic Chondrocytes.

Qiang He,Jianbing Ma,Wei Lei,Caihong Sun

doi:10.1155/2017/4601959

Abstract

Recently, Suppressor of Cytokine Signaling 1 (SOCS1) was identified as a potential therapeutic target for osteoarthritis (OA) treatment. However, the mechanisms and signaling pathways of SOCS1 in the regulation of OA development are unclear. The purpose of the current study was to investigate whether interleukin- (IL-) 4 was involved in regulatory mechanism of SOCS1 in human osteoarthritic chondrocytes. First, IL-1β was used to stimulate human osteoarthritic chondrocytes isolated from the articular cartilage of OA patients undergoing total knee replacement. The protein and mRNA expression levels of SOCS1 were upregulated in IL-1β-stimulated human osteoarthritic chondrocytes compared with control cells. The knockdown of SOCS1 increased cell viability and inhibited cell apoptosis. It was also found that IL-4 expression was increased by SOCS1 silencing. Additionally, knockdown of IL-4 reduced cell viability and increased cell apoptosis of osteoarthritic chondrocytes transfected with SOCS1 siRNA. Moreover, the decreased expression of inflammatory factors induced by SOCS1 was enhanced by IL-4 knockdown. In conclusion, IL-4 signaling plays a crucial role in the regulatory functions of SOCS1 in apoptosis and inflammation in human osteoarthritic chondrocytes. These findings provide a potential therapeutic target for the clinical treatment of OA.

Highlights

Osteoarthritis (OA) is a common joint disease worldwide [1]
Knockdown of Suppressor of Cytokine Signaling 1 (SOCS1) increased cell viability, inhibited apoptosis (Figure 2), and suppressed the production of inflammatory factors (Figure 3) in IL-1βstimulated human osteoarthritic chondrocytes which were transfected with siIL-4
This study demonstrated that IL-1β stimulation increased the expression of SOCS1, and the knockdown of SOCS1 increased cell viability and inhibited cell apoptosis and expression of inflammatory cytokines

Summary

Introduction

Osteoarthritis (OA) is a common joint disease worldwide [1]. Nearly 250 million people in the world have OA of the knee and about half of individuals develop symptomatic knee OA by age 85 [2, 3]. Progressive destruction of articular cartilage (AC) is a hallmark of OA, and chondrocytes, the only resident cells in AC, play a key role via apoptosis, cytokine production, and matrix degeneration during the development of OA [4]. SOCS1 is widely expressed in various tissues and its expression is regulated by a variety of cytokines [6]. Initial studies on SOCS1 were largely focused on its negative regulation on cytokine signaling. More and more researchers have found that SOCS1 can influence the transduction of proliferation signals and plays a role in the survival, differentiation, and transformation of cells. Choi et al [8] reported that the expression of SOCS1 is increased in OA cartilage and SOCS1 inhibits IL-1β signaling in chondrocytes.

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