晚期骨关节炎患者关节软骨细胞中HIF-1α和VEGF的表达

Expression of HIF-1α and VEGF in chondrocytes of articular cartilages in human advanced osteoarthritis

目的研究低氧诱导因子1α(HIF-1α)和血管内皮生长因子(VEGF)在晚期骨关节炎(OA)患者关节软骨细胞中的表达,初步探讨HIF-1α在OA发病机制中的作用。方法选取18例晚期膝骨关节炎(KOA)接受全膝关节置换术患者的膝关节软骨组织标本,根据取材部位分为KOA负重区组(磨损较重的股骨内髁)和KOA相对非负重区组(磨损较轻的股骨外髁);另选取5例因股骨近端或股骨干肿瘤而截肢患者的正常膝关节软骨组织标本作为对照。HE和Safranin O染色下进行Mankin整体评分比较各组关节软骨组织退变程度;免疫组织化学染色检测关节软骨细胞HIF-1α和VEGF表达,比较各组HIF-1α和VEGF阳性细胞计数。结果 KOA负重区组Mankin整体评分为(12.36±0.84),显著高于KOA相对非负重区组的(7.23±0.32)和对照组的(0.88±0.15)(P<0.05)。免疫组织化学染色显示,KOA负重区组关节软骨细胞HIF-1α和VEGF阳性细胞计数分别为4.81±0.62和5.67±0.32,均显著高于KOA相对非负重区组和对照组(分别为2.37±0.68、4.87±0.33和0.78±0.14、2.02±0.45)(P<0.05)。结论晚期OA患者关节软骨细胞中HIF-1α和VEGF蛋白表达明显增加。提示上调靶基因VEGF表达是HIF-1α在OA发病中可能的调节机制。

Objective To observe the expression of hypoxia inducible factor factor-1α （HIF-1α） and vascular endothelial growth factor （VEGF） in chondrocytes of articular cartilages in human advanced osteoarthritis （OA）, and explore the role of HIF-1α in the pathogenesis of OA. Methods Articular cartilage specimens were obtained from 18 patients with knee osteoarthritis （KOA） undergoing total knee joint replacement, and KOA weight-bearing group （medial femoral condyle, with severe abrasion） and KOA relative non-weight-bearing group （lateral femoral condyle, with moderate abrasion） were divided. Besides, articular cartilage specimens from 5 patients undergoing amputation for bone malignant neoplasms of femur proximal end and shaft of femur were served as control group. HE staining, Safranin O staining and Mankin scoring were performed to observe and evaluate the histological characteristics of articular cartilages of each group, immunohistochemical staining was conducted to detect the expression of HIF-1α and VEGF in the chondrocytes of articular cartilages, and the numbers of chondrocytes with positive expression of HIF-1α or VEGF were counted. Results The Mankin score of KOA weight-bearing group （12.36±0.84） were significantly higher than those of KOA relative non-weight-bearing group （7.23±0.32） and control group （0.88±0.15） （P〈0.05）. Immunohistochemical staining revealed that the numbers of chondrocytes with positive expression of HIF-1α or VEGF in KOA weight-bearing group （4.81±0.62 and 5.67±0.32, respectively） were significantly higher than those in KOA relative non-weight-bearing group （2.37±0.68 and 4.87±0.33, respectively） and control group （0.78±0.14 and 2.02±0.45, respectively） （P〈0.05）. Conclusion The expression of HIF-1α and VEGF protein increases in chondrocytes of articular cartilages of advanced OA, and the upregulation of expression of VEGF may be the regulatory mechanism of HIF-1α in the pathogenesis of OA.