破骨细胞介导的股骨头坏死骨髓水肿疼痛及塌陷机制

Osteoclast-mediated pain and collapse mechanisms in the femoral head necrosis with bone marrow edema

目的探讨股骨头坏死(osteonecrosis of the femoral head,ONFH)出现骨髓水肿(bone marrow edema,BME)时疼痛及塌陷的病理机制。方法选取在广州中医药大学第一附属医院因ONFH行人工全髋关节置换的ARCOⅢ期病例,收集股骨头标本、临床及影像学资料。根据术前1周MR资料将股骨头标本分为BME组和non-BME组。苏木精-伊红(HE)和天狼星红染色观察股骨头标本骨组织形态结构变化;Western blotting和q-PCR检测不同区域骨组织中CTSK、RANKL、Netrin-1的半定量表达。结果①影像学及临床资料结果表明,BME组患者VAS评分明显高于对照组。②HE染色发现,两组坏死区骨质结构絮乱,存在大量空骨陷窝;BME组肉芽组织明显,硬化区(修复区)可见大量梭形成纤维细胞及炎性细胞集聚。③天狼星红染色发现,BME组坏死区及硬化区存在大量胶原纤维。④Western blotting和q-PCR结果提示,BME组患者骨组织的坏死区、硬化区和正常区Netrin-1蛋白和基因的表达均高于non-BME组(P<0.05),BME组骨组织的坏死区、硬化区破骨相关蛋白和基因表达高于non-BME组(P<0.05)。结论髋关节疼痛与股骨头坏死BME呈正相关,过度活跃的破骨细胞参与BME时塌陷的发生,其分泌的Netrin-1蛋白上调介导相关疼痛机制。

Objective To explore pain and collapse mechanisms in fosteonecrosis of the femoral head(ONFH)with bone marrow edema(BME).Methods ONFH patients at ARCOⅢstage who underwent total hip arthroplasty in the First Affiliated Hospital of Guangzhou University of Chinese Medicine were enrolled;the femoral head samples,clinical and imaging data were collected.These patients were divided into BME group and non-BME group according to the MR data in one week preoperative.Hematoxylin-eosin and Sirius red staining were performed to observe the morphological changes in bone tissue of femoral head specimens.Western blotting and qPCR were used to semi-quantitatively analyze the expression levels of CTSK,RANKL,and Netrin-1 proteins and mRNA in different regions of the bone tissue.Results Clinical and imaging data showed that ONFH patients with BME had significantly higher scores of VAS than ONFH patients without BME.Hematoxylin-eosin staining showed that bone structure disorder and a large number of empty bone lacunae were found in the necrotic areas in both groups,but there exited significant granulation tissue in the BME group,and spindle-shaped fibroblastic cells and inflammatory cells aggregated in the repaired region.Sirius red staining revealed the necrotic and sclerotic areas were accumulated with many collagenous fiber in the BME group.The results of Western blotting and qPCR showed that Netrin-1 expressions in the necrotic,sclerotic and health areas in the BME group were higher than those in the non-BME group(P<0.05),while osteoclast related proteins and mRNA expressions of the necrotic and sclerotic areas in the BME group was higher than those in the non-BME group(P<0.05).Conclusion All these findings indicated that hip pain was positively correlated with femoral head necrosis with BME,hyperactive osteoclasts participated in the femoral head collapse with BME,and the upregulated expression of Netrin-1 mediated the pain mechanism.