Department of Orthopedics and Spine Surgery, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
Laboratory of Spinal and Spinal Cord Injury Regeneration and Repair, The First Affiliated Hospital of Anhui Medical University, 218 Jixi Road, Hefei, 230022, Anhui, China.
Eur J Med Res. 2024 Mar 25;29(1):196. doi: 10.1186/s40001-024-01784-w.
Intervertebral disc degeneration (IVDD) is a major cause of morbidity and disability. Our study aimed to investigate the potential of cartilage oligomeric matrix protein (COMP) and ADAMTS7 (A disintegrin and metalloproteinases with thrombospondin motifs 7) as biomarkers for IVDD together with their functional relationship.
IVD tissues and peripheral blood samples were collected from IVDD rabbit models over 1-4 weeks. Tissues and blood samples were also collected from clinical patients those were stratified into four equal groups according to Pfirrmann IVDD grading (I-V) with baseline data collected for each participant. COMP and ADAMTS7 expression were analyzed and biomarker characteristics were assessed using linear regression and receiver operating curve (ROC) analyses.
COMP and ADAMTS7 expression increased in tissues and serum during IVDD progression. Serum COMP (sCOMP) and serum ADAMTS7 (sADAMTS7) levels increased in a time-dependent manner following IVD damage in the rabbit model while significant positive correlations were detected between sCOMP and sADAMTS7 and Pfirrmann grade in human subjects. ROC analysis showed that combining sCOMP and sADAMTS7 assay results produced an improved diagnostic measure for IVDD compared to individual sCOMP or sADAMTS7 tests. In vitro assays conducted on human cell isolates revealed that COMP prevented extracellular matrix degradation and antagonized ADAMTS7 expression although this protective role was uncoupled under microenvironmental conditions mimicking IVDD.
Increases in circulating COMP and ADAMTS7 correlate with IVDD progression and may play regulatory roles. Assays for sCOMP and/or sADAMTS7 levels can discriminate between healthy subjects and IVDD patients, warranting further clinical assessment.
椎间盘退变（IVDD）是发病率和致残率的主要原因。我们的研究旨在探讨软骨寡聚基质蛋白（COMP）和 ADAMTS7（解整合素和金属蛋白酶与凝血酶反应蛋白 7）作为 IVDD 生物标志物的潜力及其功能关系。
收集 1-4 周 IVDD 兔模型的椎间盘组织和外周血样本。根据 Pfirrmann IVDD 分级（I-V）将临床患者的组织和血液样本分为四等份，对每位患者进行基线数据采集。使用线性回归和接收者操作曲线（ROC）分析分析 COMP 和 ADAMTS7 的表达，并评估生物标志物特征。
COMP 和 ADAMTS7 的表达在组织和血清中随着 IVDD 的进展而增加。兔模型中 IVDD 后，血清 COMP（sCOMP）和血清 ADAMTS7（sADAMTS7）水平呈时间依赖性增加，而在人类受试者中，sCOMP 和 sADAMTS7 与 Pfirrmann 分级之间存在显著的正相关关系。ROC 分析表明，与单独的 sCOMP 或 sADAMTS7 检测相比，联合 sCOMP 和 sADAMTS7 检测结果可产生改善的 IVDD 诊断措施。在体外对人细胞分离物进行的检测表明，COMP 可防止细胞外基质降解并拮抗 ADAMTS7 的表达，尽管在模拟 IVDD 的微环境条件下，这种保护作用被解除。
循环 COMP 和 ADAMTS7 的增加与 IVDD 的进展相关，可能发挥调节作用。sCOMP 和/或 sADAMTS7 水平的检测可以区分健康受试者和 IVDD 患者，值得进一步临床评估。
