血清中骨关节炎生物标记物与关节软骨早期损伤关系

The relationship between serum biomarkers of osteoarthritis and the severity of cartilage lesions in human knee joints

目的探讨血清中6种OA相关生物标记物与关节软骨损伤的关系。方法本研究共纳入2013年6月至12月入住我院关节外科79例患者。其中男性36例，女性43例，平均年龄（42±17）岁。膝OA患者共23例，其中11例行人工膝关节表面置换，12例行关节镜下膝关节清理术；因外伤致前交叉韧带断裂行前交叉韧带重建患者28例，半月板损伤患者28例。关节软骨损伤评分依据关节镜下0uterbridge软骨损伤评分。采用ELISA试验进行检测以上患者血清中6种生物标记物：软骨寡聚基质蛋白（COMP），Ⅱ型胶原羧基端端肽（CTX—Ⅱ），MMP-3，透明质酸，Ⅲ型前胶原氨基端前肽（PⅢNP），超氧化物歧化酶（SOD）。计量资料采用；挡表示，多组间比较采用单因素方差分析，两因素间相关性分析采用Spearman相关分析。结果COMP、CTX—11、MMP-3、透明质酸、PⅢNP在血清中的浓度随着软骨损伤的程度加重有逐渐升高的趋势，尤其在Outerbridge评分4分组时[COMP（8815±2225）ng／ml；透明质酸（458±158）ng/ml；CTX-Ⅱ（1．82±0．87）ng／ml；MMP-3（54±12）n∥ml；PmNP（4．70±1．06）ng／m1]浓度最高（P〈0．05），而SOD则随着软骨损伤的程度加重而逐渐降低，在Outerbridge评分4分组SOD[（103±11）U／m1]浓度最低（P〈0．05）。COMP、CTX-Ⅱ、MMP-3、透明质酸、PⅢNP与关节软骨损伤程度均呈正相关，其中COMP的相关性最高（r=-0．721，P〈0．01）。SOD与关节软骨损伤程度呈负相关（r=-0．593，P〈0．01）。透明质酸和COMP在轻度软骨损伤患者组（Outerbridge评分1分组和Outerbridge评分2分组）明显升高（P〈0．05），且与年龄、性别、BMI、发病时间呈弱相关性。结论血清中COMP、CTX-Ⅱ、MMP-3、透明质酸、PmNP、SOD等OA相关生物标记物与软骨损伤程度有一定相关性，只有COMP和透明质酸可用于关节软骨早期损伤的诊断。

Objective To evaluate the relationship between six serum biomarkers of osteoarthritis （OA） and the severity of cartilage lesions in human knee joints. Methods Seventy-nine patients [36 men and 43 women, average age was （42±17） yd] who had undergone knee arthroseopy or total knee replacement were enrolled into this study. Cartilage damage was classified during arthroscopy or direct surgical observation using the Outerhridge cartilage damage scoring system. Six serum samples were assessed for levels of the following biomarkers： cartilage oligomerie matrix protein （COMP）, cartilage type Ⅱ collagen C-telopeptide （CTX-Ⅱ ）, matrix metalloproteinase-3 （MMP-3）, type Ⅲ collagen N-propeptide （Pm NP）, hyaluronic acid （HA）, super- oxide dismutase （SOD）. One-way analysis of variance （ANOVA） was used for inter-group comparisons. Nonparametric Spearman rank correlation coefficient was used for correlation analysis. Results The serum concentrations of COMP, CTX- Ⅱ , MMP-3, HA, P m NP tended to increase with cartilage damage [COMP （8 815±2 225） ng/ml; HA （458±158） ng/ml; CTX-Ⅱ （1.82±0.87） ng/ml; MMP-3 （54±12） ng/ml; PⅢ NP （4.70±1.06） ng/ml]. On the contrary, SOD tended to decrease with cartilage damage and the levels in Outerbridge score 4 group SOD [（103±11） U/ml] was the least compared to other groups （P〈0.05）. There were no statistical significant differences were found between Outerbridge score 0, 1, 2, 3 group in CTX-Ⅱ, MMP-3, PⅢ NP and SOD. HA and COMP were found to increase significantly in the early cartilage lesion groups （Outerbridge score 1 and 2 respectively）. There was a strongest correlation between COMP and the severity of cartilage lesion （r= 0.721, P〈0.01）. No significant clinical relevant relationships between HA, COMP concentrations and a variety of clinical features could be found. Conclusion The six serum biomarkers have moderate to strong COMP and HA can be used to help detect early