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Role of fibroblast growth factor 8 (FGF8) in animal models of osteoarthritis.

Authors: Uchii, M  Tamura, T  Suda, T  Kakuni, M  Tanaka, A  Miki, I 
Citation: Uchii M, etal., Arthritis Res Ther. 2008;10(4):R90. Epub 2008 Aug 12.
Pubmed: (View Article at PubMed) PMID:18699993
DOI: Full-text: DOI:10.1186/ar2474

INTRODUCTION: 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. CONCLUSION: 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.


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CRRD Object Information
CRRD ID: 2314157
Created: 2009-11-03
Species: All species
Last Modified: 2009-11-03
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.