β-连环蛋白在膝关节原发性骨关节炎关节软骨中的表达

EXPRESSION OF β-CATENIN IN ARTICULAR CARTILAGE OF KNEE PRIMARY OSTEOARTHRITIS

目的通过检测β-连环蛋白(β-catenin)在膝关节原发性骨关节炎(osteoarthritis,OA)不同退变程度关节软骨中的表达,探讨其在原发性膝关节OA发生与发展中的作用。方法取2010年10月-2011年5月行人工全膝关节置换术的40例OA成年患者及10例创伤后行截肢术及股骨髁骨折成年患者自愿捐赠的膝关节软骨,于股骨髁切取包含全层软骨及少量软骨下骨组织块进行实验。组织切片行固绿-番红O染色,观察软骨退变情况,参照改良Mankin评分标准对软骨标本进行分级;行免疫组织化学染色及Western blot检测不同软骨组织中β-catenin表达。结果根据改良Mankin评分标准进行分级:正常软骨10例,轻度退变12例,中重度退变28例。组织学观察见轻度退变软骨浅表层裂隙形成,软骨细胞数减少,排列紊乱,潮线复制;中重度退变软骨深层裂隙形成,软骨细胞数目显著减少,成簇,甚至全层缺失。正常软骨中β-catenin表达呈阴性;OA软骨均有表达,主要位于细胞核,中重度退变软骨表达显著多于轻度退变软骨(P<0.05)。结论β-catenin与膝关节原发性OA发病机制及病情进展程度密切相关,其机制可能是Wnt/β-catenin信号通路活化后促进炎性基因转录,导致关节软骨破坏。

Objective To investigate the role of β-catenin in pathogenesis and progression of knee primaryosteoarthritis （OA） by detecting the expression of β-catenin. Methods Between October 2010 and May 2011, 40 cartilage specimens were collected from adult knee primary OA patients undergoing total knee arthroplasty and 10 cartilage specimens from adult patients suffering from amputation and femoral condylar fracture. All cartilage samples were taken out from femoralcondylar. The decalcified paraffin-embedded sections were prepared and stained with fast green-safranin O to observe the degeneration of cartilage, then the modified Mankin scale was used to classify the degeneration. The expression of β-catenin was detected by the immunohistochemistry staining and Western blot. Results According to the Mankin scale, 10 cases had normal cartilage, 12 had mild degenerative cartilage, and 28 had moderate to severe degenerative cartilage. The histologicalobservation showed the mild degenerative cartilage characterized by fissures in the superficial zone of the articular cartilage, decreased chondrocytes, arrangement disorder, and duplicated tidemark; and the moderate to severe degenerative cartilage characterized by fissures in the deep zone of the articular cartilage, obviously decreased chondrocytes and cluster, and even full- thickness cartilage defect. The β-catenin did not expressed in normal articular cartilage; but it expressed in the degenerativecartilage, and the expression was significantly higher in the moderate to severe degenerative cartilage than in mild degenerative cartilage （P 〈 0.05）. Conclusion β-catenin plays a significant role in the pathogenesis and progression of knee primary OA, and the mechanism may be the activation of Wnt/β-catenin signaling pathway, which promotes transcription of inflammatory genes and leads to the destruction of articular cartilage.