Sheu S.-Y.Ho S.-R.JUI-SHENG SUNChen C.-Y.Ke C.-J.2020-02-072020-02-0720151472-6882https://www.scopus.com/inward/record.uri?eid=2-s2.0-84939153458&doi=10.1186%2fs12906-015-0520-z&partnerID=40&md5=93cfe3dac0e421491ad2c3a19bd088b5https://scholars.lib.ntu.edu.tw/handle/123456789/455314Background: 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. 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. Methods: Chondrocytes 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. Results: Interleukin-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. Conclusion: In 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. ? 2015 Sheu et al.; licensee BioMed Central.[SDGs]SDG3aggrecanase 2; collagen type 2; collagenase 3; ecdysterone; hypoxia inducible factor 2alpha; interleukin 1beta; stromelysin; basic helix loop helix transcription factor; collagen type 2; collagenase 3; cytokine; ecdysterone; endothelial PAS domain-containing protein 1; interleukin 1beta; stromelysin; transcription factor; animal cell; animal tissue; Article; articular cartilage; cartilage cell; cell viability; controlled study; down regulation; mouse; nonhuman; osteoarthritis; protein expression; signal transduction; tissue metabolism; animal; arthropod; articular cartilage; cartilage; cell culture; drug effects; gene expression; genetics; Institute for Cancer Research mouse; male; metabolism; osteoarthritis; synovium; Animals; Arthropods; Basic Helix-Loop-Helix Transcription Factors; Cartilage; Cartilage, Articular; Cells, Cultured; Chondrocytes; Collagen Type II; Cytokines; Down-Regulation; Ecdysterone; Gene Expression; Interleukin-1beta; Male; Matrix Metalloproteinase 13; Matrix Metalloproteinase 3; Mice, Inbred ICR; Osteoarthritis; Synovial Membrane; Transcription Factorsjournal article10.1186/s12906-015-0520-z256170572-s2.0-84939153458