Section of Orthopaedic Surgery, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
J Orthop Res. 2010 Nov;28(11):1502-6. doi: 10.1002/jor.21165.
We investigated the effect of weekly intra-articular injections of bone morphogenetic protein-7 (BMP-7) on prevention of progression of existing cartilage degeneration in an osteoarthritis model in rabbits. An anterior cruciate ligament transection (ACLT) model was used to create a progressive osteoarthritis model. BMP-7 was intra-articular injected weekly into the right knee and PBS into the left knee from 4 weeks after ACLT. Both sides of the knees were compared macroscopically, histologically, immunohistochemically, and by micro CT. Macroscopically, fibrillation in the femoral condyle was observed 4 weeks after ACLT. In the control knees, cartilage degeneration further progressed throughout the 12-week period. In the BMP-7 treated knee, osteoarthritis progression was milder than in the control knees. Histologically, safranin-O staining was decreased in the surgical knees at 4 weeks. Obvious erosions in both medial and lateral condyles were revealed in the control knees at 12 weeks, while cartilage matrix was predominantly retained in the BMP-7 treated knees. The macroscopic and microscopic OA score in the BMP-7 treated knee was better than that in the control in each rabbit. Immunohistochemical analysis demonstrated that both type II collagen and BMP-7 were more expressed in cartilage treated with BMP-7. Micro CT analysis showed that osteophytes were smaller in the BMP-7 treated knee compared to that of the control. Weekly intra-articular injections of BMP-7 inhibited progression of existing cartilage degeneration.
我们研究了每周向兔骨关节炎模型关节内注射骨形态发生蛋白 7(BMP-7)对预防现有软骨退变进展的影响。采用前交叉韧带切断(ACLT)模型构建进行性骨关节炎模型。在 ACLT 后 4 周开始,每周向右侧膝关节内注射 BMP-7,向左侧膝关节内注射 PBS。比较双侧膝关节的大体、组织学、免疫组织化学和 micro CT 表现。大体观察发现,ACLT 后 4 周股骨髁出现纤维性颤动。在对照组膝关节中,软骨退变在整个 12 周内进一步进展。在 BMP-7 治疗的膝关节中,骨关节炎进展较对照组膝关节轻。组织学观察发现,4 周时手术膝关节番红 O 染色减少。对照组膝关节在 12 周时内侧和外侧髁均出现明显侵蚀,而 BMP-7 治疗的膝关节中软骨基质主要保留。在每只兔子中,BMP-7 治疗的膝关节的大体和显微镜下 OA 评分均优于对照组。免疫组织化学分析显示,BMP-7 治疗的软骨中 II 型胶原和 BMP-7 的表达均增加。Micro CT 分析显示,与对照组相比,BMP-7 治疗的膝关节中的骨赘较小。每周关节内注射 BMP-7 可抑制现有软骨退变的进展。