Expression of hypoxia-inducible factor 2 alpha and vascular endothelial growth factor in chondrocytes of articular cartilages in human osteoarthritis

doi:10.3969/j.issn.2095-4344.2015.02.008

Abstract

Abstract:

BACKGROUND: Studies have found that vascular endothelial growth factor and hypoxia inducible factor are involved in the development process of osteoarthritis, but their correlation is rarely reported.
OBJECTIVE: To observe the expression and correlation of hypoxia inducible factor-2α and vascular endothelial growth factor in chondrocytes of articular cartilages in human osteoarthritis．
METHODS: Articular cartilage specimens were collected from 50 patients with knee osteoarthritis undergoing total knee joint replacement. According to the joint Kellgren-Lawrance (K-L) X-ray grouping classification standard, there were 18 cases of K-LIII level and 32 cases of K-LIV level. Besides, articular cartilage specimens from 10 patients undergoing amputation for legs tumor or traffic accident served as control group. Hematoxylin-eosin staining, Safranin O-Fast Green 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 hypoxia inducible factor-2α and vascular endothelial growth factor in chondrocytes of articular cartilages, and their correlations were analyzed.
RESULTS AND CONCLUSION: The Mankin score of K-LIV group was significantly higher than those of K-LIII group and control group. Immunohistochemical staining revealed that the number of chondrocytes with positive expression of hypoxia inducible factor-2α or vascular endothelial growth factor in K-LIV group was significantly higher than that in K-LIII group and control group (P < 0.05). The expression of hypoxia inducible factor-2α and vascular endothelial growth factor increased in chondrocytes of articular cartilages of osteoarthritis patients, and to up-regulate the expression of vascular endothelial growth factor may be the regulatory mechanism of hypoxia inducible factor-2αin the pathogenesis of osteoarthritis．

中国组织工程研究杂志出版内容重点：组织构建；骨细胞；软骨细胞；细胞培养；成纤维细胞；血管内皮细胞；骨质疏松；组织工程

全文链接：

Key words: Osteoarthritis, Cartilage, Articular, Hypoxia-Inducible Factor 1, Vascular Endothelial Growth Factors

CLC Number:

R318

Liu Feng, Peng Hao, Zhou Jian-lin, Fang Hong-song, Deng Shuang, Yang Xiao, Weng Jin-qing. Expression of hypoxia-inducible factor 2 alpha and vascular endothelial growth factor in chondrocytes of articular cartilages in human osteoarthritis[J]. Chinese Journal of Tissue Engineering Research, 2015, 19(2): 201-206.

Figures/Tables 2

2.1 实验标本数量分析 60例实验材料均进入结果分析，无脱落例数，合格率100%。 2.2 膝关节软骨组织苏木精-伊红染色观察结果正常对照组：膝关节软骨表面光滑，表层、移行层、放射层、钙化层各层结构清晰，各层软骨细胞排列有序(见图1A)；潮线清晰、完整、规则、呈波浪状(见图1B)。 K-L Ⅲ级组：4层细胞层次可大体辨出，关节软骨表层不规则，可见明显的溃疡病变，软骨细胞变性、坏死、脱落、排列紊乱(如图1C)；潮线扭曲，起伏增大或双层潮线；囊腔样结构(Weichselbaum’s陷窝)形成(见图1D)。 K-L Ⅳ级组：4层细胞层次模糊不清，可见大量关节软骨细胞坏死脱落(见图1E)，潮线向软骨层推进，严重扭曲、断裂甚至消失(见图1F)，血管组织侵入钙化层，囊腔样结构大量出现。 2.3 膝关节软骨组织safranin O-Fast Green染色观察结果正常对照组膝关节软骨表面光滑，着色均匀；K-L Ⅲ级组关节软骨表面毛糙，有裂隙出现，染色减少，部分层面出现失染现象；K-L Ⅳ级组关节软骨表面粗糙，溃疡病变明显，软骨深放射层染色减少或缺失，部分钙化层软骨染色缺失，骨赘生长区呈强着色。见图2。 2.4 膝关节软骨损害的组织学评分结果实验组和正常对对照组进行Mankin整体评分，正常对照组、K-L Ⅲ级组、K-L Ⅳ级组Mankin整体评分结果分别为0.92±0.35，8.89±0.52，12.13±0.26，进行统计学分析结果表明，K-L Ⅳ级组Mankin整体评分高于K-L Ⅲ级组和正常对照组，差异有显著性意义(P < 0.05)。 2.5 软骨细胞低氧诱导因子2α和血管内皮生长因子免疫组织化学染色结果各组低氧诱导因子2α和血管内皮生长因子免疫组织化学染色结果见图3，4，各组软骨细胞表达低氧诱导因子2α和血管内皮生长因子的细胞分数显示；正常对照组、K-L Ⅲ级组、K-L Ⅳ级组低氧诱导因子2α阳性细胞计数分别为0.84±0.19，2.86±0.71，4.23±0.58，统计学分析结果表明，K-L Ⅳ级组阳性细胞计数高于K-L Ⅲ级组和正常对照组(P < 0.05)；正常对照组、K-L Ⅲ级组、K-L Ⅳ级组血管内皮生长因子阳性细胞计数分别为2.25±0.32、4.92±0.21、5.16±0.44，统计学分析表明，K-LIV级组阳性细胞计数高于K-L Ⅲ级组和正常对照组(P < 0.05)。"

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