title: Role of fibroblast growth factor 8 (FGF8) in animal models of osteoarthritis.
abstract: BACKGROUND
  Fibroblast growth factor 8 (FGF8) is isolated as an androgen-induced growth factor, and has recently been shown to contribute to limb morphogenesis. The aim of the present study was to clarify the role of FGF8 in animal models of osteoarthritis (OA).
  
  
  METHODS
  The expression of FGF8 in the partial meniscectomy model of OA in the rabbit knee was examined by immunohistochemistry. The effect of intraperitoneal administration of anti-FGF8 antibody was tested in a model of OA that employed injection of monoiodoacetic acid or FGF8 into the knee joint of rats. The effect of FGF8 was also tested using cultured chondrocytes. Rabbit articular chondrocytes were treated with FGF8 for 48 hours, and the production of matrix metalloproteinase and the degradation of sulfated glycosaminoglycan in the extracellular matrix (ECM) were measured.
  
  
  RESULTS
  The expression of FGF8 in hyperplastic synovial cells and fibroblasts was induced in the meniscectomized OA model, whereas little or no expression was detected in normal synovium. Injection of FGF8 into rat knee joints induced the degradation of the ECM, which was suppressed by anti-FGF8 antibody. In the monoiodoacetic acid-induced arthritis model, anti-FGF8 antibody reduced ECM release into the synovial cavity. In cultured chondrocytes, FGF8 induced the release of matrix metalloproteinase 3 and prostaglandin E2, and caused degradation of the ECM. The combination of FGF8 and IL-1alpha accelerated the degradation of the ECM. Anti-FGF8 antibody suppressed the effects of FGF8 on the cells.
  
  
  CONCLUSIONS
  FGF8 is produced by injured synovium and enhances the production of protease and prostaglandin E2 from inflamed synoviocytes. Degradation of the ECM is enhanced by FGF8. FGF8 may therefore participate in the degradation of cartilage and exacerbation of osteoarthritis.
authors.affiliation: Pharmaceutical Research Center, Kyowa Hakko Kogyo Co, Ltd, Sunto, Shizuoka, Japan.
authors.forename: Masako
authors.initials: M
authors.lastname: Uchii
authors.forename: Tadafumi
authors.initials: T
authors.lastname: Tamura
authors.forename: Toshio
authors.initials: T
authors.lastname: Suda
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kakuni
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Ichiro
authors.initials: I
authors.lastname: Miki
mesh_terms: D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D005109:Extracellular Matrix / Q000378:metabolism; D051524:Fibroblast Growth Factor 8 / Q000009:adverse effects / Q000378:metabolism* / Q000494:pharmacology; D006025:Glycosaminoglycans / Q000378:metabolism; D007270:Injections, Intra-Articular; D019807:Iodoacetic Acid / Q000009:adverse effects; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020370:Osteoarthritis, Knee / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D006025:Glycosaminoglycans; D051524:Fibroblast Growth Factor 8; C013786:A73025; D019278:Matrix Metalloproteinase 3; D015232:Dinoprostone; D019807:Iodoacetic Acid