叠加造模后膝关节骨密度改变及软骨基质金属蛋白酶-13的表达

Changes of bone mineral density around the knee joint and expression of matrix metalloproteinase-13 in the joint cartilage of additive osteoarthritis models

目的目前,骨关节炎(osteoarthritis,OA)的动物模型多根据某一致病因素而设计,而OA是综合因素的临床过程。文中评价叠加法制作OA模型的可行性,探讨造模后膝关节骨密度(bone mineral density,BMD)改变及软骨基质金属蛋白酶-13(matrixmetalloproteinase,MMP-13)的表达。方法实验组30只兔行结扎股静脉并切断腓肠肌内外侧头造模,术后4、8、12周测量膝关节4个目的区(ROI)BMD后处死动物。对照组10只12周处死。取胫骨髁关节软骨作组织学、免疫组化定量分析。结果造模后4周可见软骨面粗糙。8周有滑膜增生,软骨面纤维化、糜烂,簇聚肥大软骨细胞。12周出现软骨面剥脱,骨质裸露,骨赘形成等。造模后4周R2和R3区BMD增高,R4区于8周BMD下降。4周时软骨MMP-13平均光密度(average optical density,AOD)升高是对照组的4倍,后迅速下降,12周仍较对照组高。结论叠加法制作OA模型,效果确实,简单易行。造模后不同目的区BMD有改变,关节不稳、应力改变是其主要原因。MMP-13早期明显升高,提示MMP-13可能主要在OA早期起作用。

Objective In the present time,the animal model of osteoarthritis（OA） is mostly designed according to a specific pathogenic factor,although the disease is multi-factorial clinically.This study aimed to evaluate the addition method for the establishment of an animal OA model and observe the changes in bone mineral density（BMD） around the knee joint and the expression of matrix metalloproteinase-13（MMP-13） in the joint cartilage of the OA model.Methods We made OA models in 30 New Zealand mature rabbits by ligation of the femoral vein and abscission of the gastroenemius,and measured the BMD of the four regions of interest（ROI） by dual X-ray energy absorptiometry at 4,8 and 12 weeks after the operation.The cartilage near the medial tibial plateau was obtained for immunohistochemical and morphometric analyses.Results The OA models exhibited rough articular facets at 4 weeks,hyperplastic synovium,fibroplastic and erosive cartilage and clustered hypertrophic cells at 8 weeks,and cartilage exfoliation,bone exposure and osteophyma formation at 12 weeks.BMD increased in Regions 2 and 3 at 4 weeks and decreased in Region 4 at 8 weeks.The average optical density（AOD） of MMP-13 was approximately four times that of the control group at 4 weeks,which decreased rapidly afterwards,but remained higher than that of the control at 12 weeks.Conclusion The addition method is a good and easy way to establish the OA model,which could fully reflect the whole process of degeneration of the cartilage in OA.Joint instability and stress are the main reasons for the changes of BMD in different regions.MMP-13 may play an important role in the early stage of OA.