The short-term therapeutic effect of recombinant human bone morphogenetic protein-2 on collagenase-induced lumbar facet joint osteoarthritis in rats.
OBJECTIVE
To determine whether an intra-articular injection of recombinant human bone morphogenetic protein-2 (rhBMP-2) alleviates cartilage degradation in a rat model of osteoarthritis (OA) of the lumbar facet joint.


METHODS
The right-side facet joint OA model was created by an intra-articular injection of collagenase (type II) 2 weeks before treatment. The OA rats were divided into four groups: (1) no treatment, or intra-articular injection of either (2) saline, (3) rhBMP-2 10 ng, or (4) rhBMP-2 100 ng. The left-side facet joint served as the normal control. At 3 and 6 weeks after treatment, histological analyses were performed on the cartilage, synovium, subchondral bone and bone marrow. The cartilage and synovium were graded using a modified Mankin score and a synovium score system. Extracellular type II collagen was evaluated by immunohistochemistry.


RESULTS
Intra-articular injection of collagenase causes OA-like changes in the facet joint. OA rats treated with rhBMP-2 at both dosages tested showed reduced severity of their cartilage lesions compared with untreated and saline-treated groups. There was a statistically significant difference in the modified Mankin score compared to the untreated and saline-treated groups. However, some rhBMP-2-treated rats at the higher dose (100 ng) showed, as a side effect, joint space obliteration caused by cartilage overgrowth. Also OA rats treated with 100 ng of rhBMP-2 displayed a significant synovium reaction at 3 weeks compared with that in other groups. Immunohistochemical analysis showed that treatment with rhBMP-2 significantly increased the content of type II collagen.


CONCLUSIONS
This study demonstrates the potential efficacy of rhBMP-2 in the alleviation of arthritic changes in a rat model of OA of the lumbar facet joint. However, treatment with a high dosage of rhBMP-2 caused adverse side effects in some animals.
Yeh
T-T
TT
Graduate Institute of Medical Science, National Defense Medical Center, Taipei, Taiwan, ROC.
Wu
S-S
SS
Lee
C-H
CH
Wen
Z-H
ZH
Lee
H-S
HS
Yang
Z
Z
Nimni
M E
ME
Han
B
B
D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D002358:Cartilage, Articular / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D020784:Matrix Metalloproteinase 8 / Q000008:administration & dosage / Q000009:adverse effects*; D010003:Osteoarthritis / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D013194:Staining and Labeling; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology / Q000627:therapeutic use*; D021801:Zygapophyseal Joint / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D024043:Collagen Type II; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2; D020784:Matrix Metalloproteinase 8