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Open Access Highly Accessed Research article

Weekly intra-articular injections of bone morphogenetic protein-7 inhibits osteoarthritis progression

Masaya Hayashi1, Takeshi Muneta1, Young-Jin Ju1, Tomoyuki Mochizuki2 and Ichiro Sekiya2*

Author affiliations

1 Section of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan

2 Section of Cartilage Regeneration, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan

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Citation and License

Arthritis Research & Therapy 2008, 10:R118  doi:10.1186/ar2521

Published: 30 September 2008

Abstract

Introduction

We investigated the ability of a weekly intra-articular injection of bone morphogenetic protein (BMP)-7 to prevent osteoarthritis in rabbits with anterior cruciate ligament transections.

Methods

First, 36 knee joints were randomly divided into four groups: 50, 500, 5,000 ng BMP-7, and control. Knee cartilage was evaluated at 4, 8, and 12 weeks. Then, in order to control for individual differences, 500 ng BMP-7 was injected into one knee and phosphate-buffered saline (PBS) into the other, and the two knees were compared at 4, 8, and 12 weeks (n = 5). For pharmacokinetic analysis, cartilage was harvested at 1 hour and 1, 2, 4, and 7 days after knee injection of 500 ng BMP-7 or PBS (n = 3).

Results

Histological scores in the 500 and 5,000 ng BMP-7 groups were significantly better than those in the other groups at 12 weeks. Matched pair analysis demonstrated that both macroscopic and histological scores in the 500 ng BMP-7 group were better than those in the control group. Immunohistochemical analysis revealed higher BMP-7 expression by chondrocytes in the BMP-7 injected knees. Histology of whole knee and quantitative micro computed tomography analysis showed that weekly injections of 500 ng BMP-7 did not induce synovial fibrosis, ectopic bone, or osteophyte formation. As detected by enzyme-linked immunosorbent assay, BMP-7 concentration in the cartilage tissue was still higher in the BMP-7 treated group 7 days after the injection.

Conclusions

Weekly intra-articular injections of BMP-7 inhibited progression of osteoarthritis. Obvious adverse effects were not observed. BMP-7 concentration and expression in cartilage were still higher 7 days after injection.