Email updates

Keep up to date with the latest news and content from Arthritis Research & Therapy and BioMed Central.

Open Access Research article

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

Masako Uchii1, Tadafumi Tamura1, Toshio Suda1, Masakazu Kakuni12, Akira Tanaka3 and Ichiro Miki1*

Author Affiliations

1 Pharmaceutical Research Center, Kyowa Hakko Kogyo Co., Ltd, 1188 Shimotogari, Nagaizumi, Sunto, Shizuoka 411-8731, Japan

2 Present address: PhoenixBio Co., Ltd, 3-4-1 Kagamiyama, Higashi-Hiroshima, Hiroshima 739-0046, Japan

3 Department of Pathology, Jichi Medical University, 3311-1 Yakushiji, Shimotsuke, Tochigi 329-0498, Japan

For all author emails, please log on.

Arthritis Research & Therapy 2008, 10:R90  doi:10.1186/ar2474

Published: 12 August 2008

Abstract

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-1α 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.