title: Celastrol inhibits prostaglandin E2-induced proliferation and osteogenic differentiation of fibroblasts isolated from ankylosing spondylitis hip tissues in vitro.
abstract: BACKGROUND
  Heterotopic ossification on the enthesis, which develops after subsequent inflammation, is one of the most distinctive features in ankylosing spondylitis (AS). Prostaglandin E2 (PGE-2) serves as a key mediator of inflammation and bone remodeling in AS. Celastrol, a well-known Chinese medicinal herb isolated from Tripterygium wilfordii, is widely used in treating inflammatory diseases, including AS. It has been proven that it can inhibit lipopolysac-charide-induced expression of various inflammation mediators, such as PGE-2. However, the mechanism by which celastrol inhibits inflammation-induced bone forming in AS is unclear.
  
  
  OBJECTIVE
  To investigate whether celastrol could inhibit isolated AS fibroblast osteogenesis induced by PGE-2.
  
  
  METHODS
  Hip synovial tissues were obtained from six AS patients undergoing total hip replacement in our hospital. Fibroblasts were isolated, primarily cultured, and then treated with PGE-2 for osteogenic induction. Different doses of celastrol and indometacin were added to observe their effects on osteogenic differentiation. Cell proliferation, osteogenic markers, alizarin red staining as well as the activity of alkaline phosphatase were examined in our study.
  
  
  RESULTS
  Celastrol significantly inhibits cell proliferation of isolated AS fibroblasts and in vitro osteogenic differentiation compared with control groups in a time- and dose-dependent manner.
  
  
  CONCLUSIONS
  Our results demonstrated that celastrol could inhibit isolated AS fibroblast proliferation and in vitro osteogenic differentiation. The interaction of PI3K/AKT signaling and Wnt protein may be involved in the process. Further studies should be performed in vivo and animal models to identify the potential effect of celastrol on the bone metabolism of AS patients.
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guang Zhou, People's Republic of China.
authors.forename: Yu-Cong
authors.initials: YC
authors.lastname: Zou
authors.affiliation: The Third Affiliated Hospital, Guangzhou University of Traditional Chinese Medicine, Guang Zhou, People's Republic of China.
authors.forename: Xian-Wen
authors.initials: XW
authors.lastname: Yang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guang Zhou, People's Republic of China.
authors.forename: Shi-Guo
authors.initials: SG
authors.lastname: Yuan
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guang Zhou, People's Republic of China.
authors.forename: Pei
authors.initials: P
authors.lastname: Zhang
authors.affiliation: School of Traditional Chinese Medicine, Southern Medical University, Guang Zhou, People's Republic of China.
authors.forename: Yi-Kai
authors.initials: YK
authors.lastname: Li
mesh_terms: D000328:Adult; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000473:pathology; D006621:Hip Joint / Q000473:pathology*; D006801:Humans; D008297:Male; D010012:Osteogenesis / Q000187:drug effects*; D053978:Pentacyclic Triterpenes; D013167:Spondylitis, Ankylosing / Q000473:pathology*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D053978:Pentacyclic Triterpenes; D014315:Triterpenes; D015232:Dinoprostone; C050414:celastrol
keywords: ankylosing spondylitis; celastrol; fibroblasts; osteogenesis; proliferation; prostaglandin E2