The Short-Term Therapeutic Effect of Recombinant Human Bone Morphogenetic Protein-2 on Collagenase Induced Experimental Osteoarthritis of the Lumbar Facet Joint in Rats

• Main Authors: Tsu-Te Yeh, 葉祖德
• Other Authors: Shing-Sheng Wu
• Format: Others
• Language: zh-TW
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/04342959185490604627

博士 === 國防醫學院 === 醫學科學研究所 === 95 === Background: Osteoarthritis (OA) of the lumbar facet joint is one of the sources of low back pain. Even after spinal fusion or artificial disc implantation surgery, facet joint arthrosis is one of the reasons leading to unsatisfactory results. There are no references reporting on an OA model of the lumbar facet joint in rats. The therapeutic effect of recombinant human bone morphogenetic protein-2 (rhBMP-2) on the lumbar facet joint OA is still unknown. Objective: The objectives of this research were to establish an animal model to investigate primary experimental osteoarthritis of the lumbar facet joints after collagenase injection in rats, and the effects on chondrocytes apoptosis. We also want to determine whether an intra-articular injection of rhBMP-2 alleviates cartilage degradation in this model of OA of the lumbar facet joint. Methods: Collagenase (1 U, 10 U, or 50 U) or saline was intra-articularly injected into the right side lumbar facet joints. The left side facet joint served as the normal control. The cartilage, synovium and subchondral bone were examined by histological and histochemical methods at 1, 3, and 6 weeks post-injection. The cartilage and synovium were graded using the OARSI score and a synovium score system. Apoptotic cells induced by one unit of collagenase were quantified by the TUNEL method. In the rhBMP-2 treatment study, the right side facet joint OA model was created by an intra-articular injection of 5 U of collagenase two weeks before treatment. The OA rats were divided into 4 groups: 1) no treatment, or intra-articular injection of either 2) saline, 3) rhBMP-2 10 ng, or 4) rhBMP-2 100 ng. 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: The degeneration of the cartilage and changes of synovium and subchondral bone were found to be dependent on both the dose of collagenase and the time post-surgery. Apoptotic chondrocytes were significantly increased above the control group. 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 Conclusion: The lumbar facet joints subjected to collagenase developed OA-like changes. These changes can be quantified and compared. This model provides a useful tool for the further study of the pathogenesis of OA and the effects of compounds that have the potential to inhibit enzyme associated damage to cartilage cells. The potential efficacy of rhBMP-2 in the alleviation of arthritic changes of OA of the lumbar facet joint is also demonstrated. However, treatment with a high dosage of rhBMP-2 caused adverse side effects in some animals.