Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β-induced catabolic gene expression in cartilage.

Shiow-Yunn Sheu,Jui-Sheng Sun,Cherng-Jyh Ke,Ching-Yun Chen,Shin-Rong Ho

doi:10.1186/s12906-015-0520-z

Abstract

BackgroundIn osteoarthritis (OA), the imbalance of chondrocytes’ anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1β) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. The purpose of this study is to validate the effects of ecdysteroids (Ecd) on IL-1β- induced cartilage catabolism and the possible role of Ecd in treatment or prevention of early OA.MethodsChondrocytes and articular cartilage was harvested from newborn ICR mice. Ecd effect on chondrocytes viability was tested and the optimal concentration was determined by MTT assay. The effect of HIF-2α (EPAS1) in cartilage catabolism simulated by IL-1β (5 ng/ml) was evaluated by articular cartilage explants culture. The effects of Ecd on IL-1β-induced inflammatory conditions and their related catabolic genes expression were analyzed.ResultsInterleukin-1β (IL-1β) treatment on primary mouse articular cartilage explants enhanced their Epas1, matrix metalloproteinases (MMP-3, MMP-13) and ADAMTS-5 genes expression and down-regulated collagen type II (Col2a1) gene expression. With the pre-treatment of 10−8M Ecd, the catabolic effects of IL-1β on articular cartilage were scavenged.ConclusionIn conclusions, Ecd can reduce the IL-1β-induced inflammatory effect of the cartilage. Ecd may suppress IL-1β- induced cartilage catabolism via HIF-2α pathway.

Highlights

In osteoarthritis (OA), the imbalance of chondrocytes’ anabolic and catabolic factors can induce cartilage destruction
The purpose of this study is to validate the effects of Ecd on IL-1β- induced cartilage destruction and the possible role of Ecd in treatment or prevention of early OA
Ecd pre-treatment reduce the catabolic effect of IL-1β on the cartilage explants The catabolic effect of IL-1β on cartilage explants are mediated via hypoxia-inducible factor-2α (HIF-2α)–induced expression of MMP3, MMP13

Summary

Introduction

In osteoarthritis (OA), the imbalance of chondrocytes’ anabolic and catabolic factors can induce cartilage destruction. Interleukin-1 beta (IL-1β) is a potent pro-inflammatory cytokine that is capable of inducing chondrocytes and synovial cells to synthesize MMPs. The hypoxia-inducible factor-2alpha (HIF-2alpha, encoded by Epas1) is the catabolic transcription factor in the osteoarthritic process. An imbalance between anabolic and catabolic factors within chondrocytes may cause osteoarthritic cartilage destruction [3-5]. The hypoxia-inducible factor-2alpha (HIF2α, encoded by Epas1) is a catabolic transcription factor in the osteoarthritic process. HIF-2α directly induces chondrocytes expression of genes encoding catabolic factors, such as matrix metalloproteinases (MMP1, MMP3, MMP9, MMP12 and MMP13), aggrecanase-1 (ADA#MTS4), nitric oxide synthase-2 (NOS-2) and prostaglandin-endoperoxide synthase-2 [3,4].

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