骨化三醇对大鼠骨性关节炎关节软骨及软骨下骨的影响

The effect of calcitriol on articular cartilage and subchondral bone changes in rat anterior cruciate ligament transaction

目的观察骨化三醇对大鼠前交叉韧带切断术后膝关节软骨及软骨下骨的影响,探讨软骨下骨在骨性关节炎发病中的作用。方法取SD大鼠64只分成4组,前交叉韧带切断组（ACLT组）、前交叉韧带切断＋骨化三醇给药组（ACLT＋cal组）、假手术组（sham组）、假手术＋骨化三醇给药组（sham＋cal组）,给药组术后第2天给骨化三醇0.1μg.kg-1.d^-1灌胃,ACLT组和sham组给予安慰剂灌胃,持续2周。每组分别于术后2周和10周取材,胫骨近端切片后,行HE、AB-PAS染色、MMP-13免疫组化及骨形态计量学分析。结果HE、AB-PAS染色、MMP-13免疫组化及骨形态计量学参数测量显示,2周时ACLT组与sham组相比早期有软骨下骨量减少,ACLT＋cal组较ACLT组软骨下骨量增多（P〈0.05）。10周时ACLT组软骨明显退变性改变、软骨下骨增生及MMP-13表达增强,ACLT＋cal组软骨退变及软骨下骨增生均较ACLT组减轻（P〈0.01）,MMP-13表达较ACLT组降低（P〈0.05）。结论软骨下骨在骨性关节炎病变进展中发挥重要作用,骨代谢调节剂骨化三醇可减缓OA进展中软骨下骨硬化,对关节软骨有一定保护作用。

Objective To observe calcitiol on cartilage and subchondral bone in the rat anterior cruciate ligament transaction model, and assess the role of subchondral bone in the etiology of osteoarthritis （OA） . Method Sixtyfour rats were divided into four groups： anterior cruciate ligament transacttion（ACLT）, ACLT＋ calcitiol（ ACLT ＋ cal）, sham and sham ＋ cal. After operation,rats in group ACLT ＋ caland group sham ＋ eal received calcitriol 0.1 μg/kg intragastric administrationally every day for the following 2weeks. The rats were sacrificed at 2weeks and 10weeks postsurgery, and the tibil plates were harvested which were studied in both pathohistological and bone histomorphometrie analysis. At the same time Coimmunostaining for matrix metalloproteinase13 （MMP-13） was performed to investigate the progression of cartilage degradetion. Result At 2weeks postsurgery, The bone volum in ACLT group is less than Sham group, and the bone volum is more in ACLT ＋ cal group than in ACLT group（ P 〈 0.05）. At 10weeks postsurgery, degeneration of articular cartilage in ACLT group got worse significantly, and the subchondral bone were hyperostosis. In ACLT ＋ eal group, not only the hyperostosis of subcondral bone are less than in ACLT group, the Mankin score of cartilage are lower as well（ P 〈 0.01 ）. MMP- 13 expressions were significantly higher In ACLT ＋ cal group than those in ACLT ＋ cal group （ P 〈 0.05）. Conclusion Subchondral bone plays an important role in the pathogenesis of OA. Calcitoil could be used to aggregate the subcondral bone hyperostosis in the presession of OA. It could also protect the Articular Cartilage partially.