title: Arthropod steroid hormone (20-Hydroxyecdysone) suppresses IL-1β-induced catabolic gene expression in cartilage.
abstract: BACKGROUND
  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(-8) M Ecd, the catabolic effects of IL-1β on articular cartilage were scavenged.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. amel@tmu.edu.tw.
authors.forename: Shiow-Yunn
authors.initials: SY
authors.lastname: Sheu
authors.affiliation: School of Pharmacy, College of Pharmacy, Taipei Medical University, Taipei, Taiwan. god940@gmail.com.
authors.forename: Shin-Rong
authors.initials: SR
authors.lastname: Ho
authors.affiliation: Department of Orthopedic Surgery, National Taiwan University Hospital Hsin-Chu Branch, No.25, Lane 442, Sec. 1, Jingguo Rd., Hsin-Chu City, ROC, 30059, Taiwan. drjssun@gmail.com.|Department of Orthopedic Surgery, College of Medicine, National Taiwan University, No. 1, Ren-Ai Rd., Taipei, ROC, 10051, Taiwan. drjssun@gmail.com.|Biomimetic Systems Research Center, National Chiao Tung University, Hsin-Chu City, Taiwan. drjssun@gmail.com.
authors.forename: Jui-Sheng
authors.initials: JS
authors.lastname: Sun
authors.affiliation: Institute of Biomedical Engineering, College of Engineering and College of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan. chingyun523@gmail.com.
authors.forename: Ching-Yun
authors.initials: CY
authors.lastname: Chen
authors.affiliation: Biomimetic Systems Research Center, National Chiao Tung University, Hsin-Chu City, Taiwan. fonchanwd@gmail.com.
authors.forename: Cherng-Jyh
authors.initials: CJ
authors.lastname: Ke
mesh_terms: D000818:Animals; D001181:Arthropods; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism; D002358:Cartilage, Articular / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects* / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D015536:Down-Regulation; D004441:Ecdysterone / Q000494:pharmacology*; D015870:Gene Expression; D053583:Interleukin-1beta / Q000378:metabolism*; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism; D008813:Mice, Inbred ICR; D010003:Osteoarthritis / Q000378:metabolism* / Q000517:prevention & control; D013583:Synovial Membrane / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D024043:Collagen Type II; D016207:Cytokines; D004441:Ecdysterone; D053583:Interleukin-1beta; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3; D014157:Transcription Factors; D000099162:Endothelial PAS Domain-Containing Protein 1