Department of Orthopaedic Surgery, Surgical Science, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan.
Arthritis Res Ther. 2010;12(5):R178. doi: 10.1186/ar3142. Epub 2010 Sep 24.
In this study, we investigate the efficacy of repairing an osteochondral defect in rabbit knee joints by administering bevacizumab, a humanized monoclonal anti-vascular endothelial growth factor (VEGF) antibody.
An osteochondral defect was created on the patellar groove of 20 Japanese white rabbits that were classified into two recipient groups: group B, administration of bevacizumab (100-mg intravenous injection on the day of surgery and 2 weeks later), and a control group (defect only). Rabbits were killed 1 and 3 months postoperatively. Sections were stained with safranin O. Repair sites were evaluated using the modified O'Driscoll International Cartilage Repair Society grading system. The expression of chondromodulin (ChM)-I and VEGF was evaluated using immunohistochemical analyses.
At 1 month postoperatively, the repair site in group B was filled with cartilaginous tissue. At 3 months, the repair site retained this cartilage phenotype. At 1 month in the controls, the defects were mainly filled with fibrous tissue. At 3 months, the defect was replaced by fibrous tissue and bone. Over the 3-month period, histological scores were significantly higher in group B than in the controls. At 1 month, group B showed intense positive results for ChM-I in the bottom of the repair tissue. VEGF was also identified in the same area. In the controls, no ChM-I was observed in the repair tissue. Conversely, the remodeling hypertrophic chondrocyte layer stained intensely for VEGF.
Intravenous administration of bevacizumab contributes to better repair of articular cartilage in an osteochondral defect model. We suggest the possibility of facilitating articular cartilage repair with anti-VEGF antibody rather than using cultured cells or artificial scaffolds.
本研究旨在探讨贝伐单抗（一种人源化单克隆抗血管内皮生长因子 [VEGF] 抗体）对修复兔膝关节骨软骨缺损的疗效。
在 20 只日本大白兔的髌骨关节槽处制作骨软骨缺损模型，将其分为贝伐单抗组（手术当天和 2 周后各静脉注射 100mg）和对照组（仅制作缺损）。术后 1 个月和 3 个月处死兔子。用番红 O 染色切片。采用改良 O'Driscoll 国际软骨修复学会分级系统评估修复部位。采用免疫组织化学分析评估软骨调节素（ChM）-I 和 VEGF 的表达。
术后 1 个月，贝伐单抗组修复部位充满软骨组织。术后 3 个月，修复部位仍保持软骨表型。对照组术后 1 个月缺损主要填充纤维组织，术后 3 个月缺损被纤维组织和骨替代。3 个月时，贝伐单抗组的组织学评分明显高于对照组。术后 1 个月，贝伐单抗组修复组织底部 ChM-I 呈强阳性。同一区域也检测到 VEGF。对照组修复组织未见 ChM-I。相反，重塑的肥大软骨细胞层 VEGF 染色强烈。
静脉内给予贝伐单抗有助于改善骨软骨缺损模型中关节软骨的修复。我们提出了使用抗 VEGF 抗体促进关节软骨修复的可能性，而不是使用培养细胞或人工支架。
