Weekly intra-articular injections of bone morphogenetic protein-7 inhibits osteoarthritis progression.
BACKGROUND
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.
Hayashi
Masaya
M
Section of Orthopaedic Surgery, Graduate School, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, 113-8519 Japan. hayashi.orj@tmd.ac.jp
Muneta
Takeshi
T
Ju
Young-Jin
YJ
Mochizuki
Tomoyuki
T
Sekiya
Ichiro
I
D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology; D055419:Bone Morphogenetic Protein 7 / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002356:Cartilage / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D007150:Immunohistochemistry; D007269:Injections, Intra-Arterial; D020370:Osteoarthritis, Knee / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits
D055419:Bone Morphogenetic Protein 7