中国组织工程研究

中国组织工程研究 ›› 2020, Vol. 24 ›› Issue (2): 236-241.doi: 10.3969/j.issn.2095-4344.1916

• 软骨组织构建 cartilage tissue construction • 上一篇    下一篇

膝关节骨关节炎患者软骨炎症因子表达与病变程度的相关性

邬  波1，2，马  旭1，2，柳  椰1，2，王译晗2，王佳媛2，李重阳2，焦递进2   

  1. 1沈阳市骨科医院关节外科，辽宁省沈阳市  110044；2辽宁省骨关节病重点实验室，辽宁省沈阳市  110044
  • 收稿日期:2018-12-18 修回日期:2019-01-10 接受日期:2019-03-27 出版日期:2020-01-18 发布日期:2019-12-25
  • 通讯作者: 邬波，主任医师，博士生导师，沈阳市骨科医院关节外科，辽宁省沈阳市 110044；辽宁省骨关节病重点实验室，辽宁省沈阳 110044
  • 作者简介:邬波，男，2003年中国医科大学毕业，博士生导师，主任医师，主要从事创伤骨科、脊柱与关节外科研究。

Correlation of the expression of the inflammatory cytokines and the pathological degree in patients with knee osteoarthritis

Wu Bo1, 2, Ma Xu1, 2, Liu Ye1, 2 , Wang Yihan2, Wang Jiayuan2, Li Chongyang2, Jiao Dijin2   

  1. 1Department of Joint Surgery, Shenyang Orthopedic Hospital, Shenyang 110044, Liaoning Province, China; 2Key Laboratory of Osteoarthropathy of Liaoning Province, Shenyang 110044, Liaoning Province, China
  • Received:2018-12-18 Revised:2019-01-10 Accepted:2019-03-27 Online:2020-01-18 Published:2019-12-25
  • Contact: Wu Bo, Department of Joint Surgery, Shenyang Orthopedic Hospital, Shenyang 110044, Liaoning Province, China; Key Laboratory of Osteoarthropathy of Liaoning Province, Shenyang 110044, Liaoning Province, China
  • About author:Wu Bo, Doctoral supervisor, Chief physician, Department of Joint Surgery, Shenyang Orthopedic Hospital, Shenyang 110044, Liaoning Province, China; Key Laboratory of Osteoarthropathy of Liaoning Province, Shenyang 110044, Liaoning Province, China

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摘要：

文题释义：

金属蛋白酶组织抑制因子1：是金属蛋白酶组织抑制因子家族成员，在人的细胞和组织中广泛表达，具有独特的分子特性和特征，已被证明在各种生物过程的调节中表现出多种活性，如细胞生长，凋亡和分化等。金属蛋白酶组织抑制因子1作为骨中的局部细胞因子，通过抑制成骨细胞分化和诱导成骨细胞凋亡来调节骨代谢。

Mankin评分：是学术界公认的对骨性关节炎软骨退变程度进行评价的通用标准。具体评价方法为：Ⅰ软骨结构：正常0分，表面不规则1分，血管翳形成和表面不规则2分，裂隙进入过渡层3分，裂隙进入辐射层4分，裂隙进入钙化层5分，结构完全破坏6分；Ⅱ软骨细胞：正常0分，弥漫性细胞增加1分，局部细胞增加2分，细胞数目明显减少3分；Ⅲ软骨基质染色：正常0分，轻度减少1分，中度减少2分，重度减少3分，无着色4分；Ⅳ潮线完整性：完整0分，被血管破坏1分。4项总和为Mankin评分结果，分数越高，软骨退变程度越严重。


背景：在骨性关节炎的发展过程中，导致软骨最终破坏的机制尚不清楚。研究表明，基质金属蛋白酶家族在软骨基质降解中起着重要作用。

目的：观察膝关节骨关节炎患者的基质金属蛋白酶3、金属蛋白酶组织抑制因子1表达与病变程度的相关性。

方法：研究经沈阳市骨科医院伦理委员会批准。收集行人工全膝关节置换的40例骨关节炎患者的胫骨平台，所有患者均自愿捐赠标本并签署知情同意书。根据Kellgren-Lawrence分级标准评价影像学骨关节炎的分级及分组：对照组6例；KL2级组11例；KL3级组15例；KL4级组14例。将标本行苏木精-伊红染色，采用Mankin病理评分对骨关节炎软骨病理学改变进行组织形态学评估，利用免疫组织化学方法检测各组软骨中的基质金属蛋白酶3和金属蛋白酶组织抑制因子1的水平。

结果与结论：①苏木精-伊红染色观察发现，对照组软骨层厚，软骨细胞数量多且排列整齐；KL2组软骨浅表层不平整，偶见裂隙形成；KL3组软骨层纤维化，软骨细胞排列紊乱；KL4组软骨层结构丧失，软骨细胞数量少且排列紊乱；②免疫组织化学方法检测发现，骨关节炎组基质金属蛋白酶3表达均显著高于对照组，并且骨关节炎组中KL2组、KL3组、KL4组的基质金属蛋白酶3表达呈上升趋势(均P < 0.05)；骨关节炎组金属蛋白酶组织抑制因子1的表达均显著低于对照组，并且骨关节炎组中KL2组、KL3组、KL4组的金属蛋白酶组织抑制因子1表达呈下降趋势(均P < 0.05)；③基质金属蛋白酶3表达水平与Mankin评分存在显著的正相关(r=0.899，P < 0.001)；金属蛋白酶组织抑制因子1表达水平与Mankin评分存在显著的负相关(r=-0.903，P < 0.001)；金属蛋白酶组织抑制因子1表达水平与基质金属蛋白酶3表达水平存在显著的负相关(r=-0.881，P < 0.001)； ④结果说明，骨关节炎患者关节软骨基质金属蛋白酶3和金属蛋白酶组织抑制因子1水平与病变严重程度相关，可用作评价膝关节骨关节炎病程和进展的有效指标。


ORCID: 0000-0003-3357-1523(邬波)

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

关键词: 骨性关节炎, 基质金属蛋白酶3, 金属蛋白酶组织抑制因子1, Mankin评分, 相关性分析

Abstract:

BACKGROUND: In the development of osteoarthritis, the mechanism underlying cartilage damage is still unclear. Matrix metalloproteinases have been shown to play important roles in cartilage matric degradation.

OBJECTIVE: To observe the correlation between the expression of matrix metalloproteinase 3, tissue inhibitor of metalloproteinase-1 and the pathological degree in knee osteoarthritis.

METHODS: The study was approved by the Ethics Committee of Shenyang Orthopedic Hospital. The tibial plateaus of 40 patients with knee osteoarthritis who underwent total knee arthroplasty were collected, and all patients signed the informed consents. The classification of osteoarthritis was evaluated according to Kellgren-Lawrence (KL) scale system: 11 cases of KL grade 2, 15 cases of KL grade 3, and 14 cases of KL grade 4. Control group contained six cases. Samples received hematoxylin-eosin staining. The pathological changes of knee osteoarthritis cartilage were evaluated by Mankin score. Immunohistochemical staining was used to detect the contents of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 in cartilage.

RESULTS AND CONCLUSION: (1) Hematoxylin-eosin staining results showed that in the control group, the layer of cartilage was thick, and there were abundant chondrocytes that arranged regularly. The subcutaneous layer of cartilage in the KL grade 2 group was rugged, and fissure was observed occasionally. Fibrosis of cartilage layer was visible in the KL grade 3 group, and the chondrocytes arranged in disorder. In the KL grade 4 group, the structure of cartilage layer was lost, and there were few chondrocytes that arranged irregularly. (2) Immunohistochemical staining results showed that the expression level of matrix metalloproteinase 3 in the osteoarthritis group was significantly higher than that in the control group. The expression level of matrix metalloproteinase 3 was on a rise in the KL grade 2, 3 and 4 groups (all P < 0.05). The expression level of tissue inhibitor of metalloproteinase-1 in the osteoarthritis group was significantly lower than that in the control group. The expression level of tissue inhibitor of metalloproteinase-1 was on a descent in the KL grade 2, 3 and 4 groups (all P < 0.05). (3) There was significantly positive correlation between matrix metalloproteinase 3 expression level and Mankin score (r=0.899, P < 0.001), and tissue inhibitor of metalloproteinase-1 expression level was negatively correlated with Mankin score (r=-0.903, P < 0.001). There was significantly negative correlation between tissue inhibitor of metalloproteinase-1 expression level and matrix metalloproteinase 3 expression level (r=-0.881, P < 0.001). (4) These results indicate that in the articular cartilage of patients with osteoarthritis, the expression levels of matrix metalloproteinase 3 and tissue inhibitor of metalloproteinase-1 are correlated with the pathological changes, which can be used as an effective index to evaluate the progress of knee osteoarthritis.

Key words: osteoarthritis, matrix metalloproteinase 3, tissue inhibitor of metalloproteinase-1, Mankin score, correlation analysis

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