The role of fibroblast growth factor-8 (FGF8) in animal models of osteoarthritis

Masako Uchii,Ichiro Miki,Toshio Suda,Masakazu Kakuni,Tadafumi Tamura,Akira Tanaka

doi:10.1186/ar2474

Abstract

IntroductionFibroblast 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).MethodsThe 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.ResultsThe 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-1α accelerated the degradation of the ECM. Anti-FGF8 antibody suppressed the effects of FGF8 on the cells.ConclusionFGF8 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.

Highlights

Fibroblast growth factor 8 (FGF8) is isolated as an androgen-induced growth factor, and has recently been shown to contribute to limb morphogenesis
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 extracellular matrix (ECM), which was suppressed by anti-FGF8 antibody

Summary

Introduction

Fibroblast growth factor 8 (FGF8) is isolated as an androgen-induced growth factor, and has recently been shown to contribute to limb morphogenesis. Osteoarthritis (OA) is a degenerative disease and a major cause of disability in humans. Degeneration is mainly characterized by the destruction of articular cartilage, which is composed of abundant extracellular matrix (ECM) that is rich in sulfated proteoglycan and type II collagen [1]. In OA, synovitis is believed to be a reactive process as a result of cartilage destruction and the release of ECM-degradation products in the synovial fluid [1]. Loss of the ECM is caused by the secretion of degradative enzymes from chondrocytes in response to cytokines and prostaglandin E2 (PGE2) within the joint [1,2]. Matrix metalloproteinases (MMPs) are implicated in the destruction of articular cartilage in arthritis [3]. MMP-3 is believed to be a key enzyme involved in the degradation of the ECM [4]. Levels of proMMP-3 are reported to increase in joint injury and OA [6]

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