The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis
The release of crosslinked peptides from type II collagen into human synovial fluid is increased soon after joint injury and in osteoarthritis
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DOI：
10.1002/art.11326
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发表时间：
2003-11-01
影响因子：
--
通讯作者：
Eyre, DR
中科院分区：
文献类型：
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作者：
Lohmander, LS;Atley, LM;Eyre, DR
Objective.测定关节损伤、骨关节炎（OA）或其他膝关节炎患者滑液（SF）中II型胶原蛋白（CTX-II）的交联C端肽片段的浓度。方法。使用了两个研究组：横断面组，包括健康膝关节志愿者（参考组[REF]）和假性痛风（PPA）、前交叉韧带撕裂伴或不伴半月板撕裂（INJ）或原发性膝关节OA（POA）患者;纵向组，包括关节镜软骨改变或脓毒性关节炎患者。CTX-II通过基于单克隆抗体的竞争酶联免疫吸附测定（ELISA）定量。识别肽EKGPDP的C末端作为蛋白水解新表位的抗体。用ELISA法测定聚集蛋白聚糖片段、基质金属蛋白酶1和3以及金属蛋白酶组织抑制剂I。PPA、INJ和POA患者SF中CTX-II浓度高于REF组（P < 0.001）。关节损伤后，SF中CTX-Ⅱ的平均水平在所有时间间隔均高于REF水平（P < 0.001），并在创伤后数小时内达到最高水平。在那些在纵向研究组与关节软骨损伤，CTX-II的变异系数为81%（患者之间）和64%（与患者），监测超过一年。在脓毒性关节炎患者中，SF CTX-II在症状发作时增加，峰值比基线高30倍。所有生物标志物的浓度随着治疗的成功而降低。这是第一份报告，以描述释放到SF的可溶性分子片段的成熟，交联，II型胶原蛋白（CII）在人类OA和关节损伤的降解。这些结果提供了强有力的证据表明，在关节损伤和关节炎后不久，CII软骨网络的完整性就会受到损害。CII的这种早期降解可能代表重要的治疗靶点。
Objective. To determine concentrations of crosslinked C-telopeptide fragments of type II collagen (CTX-II) in synovial fluid (SF) from patients with joint injury, osteoarthritis (OA), or other knee arthritides.Methods. Two study groups were used: a cross-sectional group, which included healthy-knee volunteers (reference group [REF]) and patients with pseudogout (PPA), an anterior cruciate ligament tear with or without a meniscus tear (INJ), or primary knee OA (POA); and a longitudinal group, which included patients with arthroscopic cartilage changes or septic arthritis. CTX-II was quantified by competition enzyme-linked immunosorbent assay (ELISA) based on a monoclonal. antibody that recognized the C-terminus of the peptide EKGPDP as a proteolytic neoepitope. Aggrecan fragments, matrix metalloproteinases 1 and 3, and tissue inhibitor of metalloproteinases I were determined by ELISAs.Results. Concentrations of CTX-II in SF were higher in patients with PPA, INJ, and POA than in the REF group (P < 0.001). After joint injury, mean levels of CTX-II in SF were increased above REF levels at all time intervals (P < 0.001), and were highest within hours after trauma. In those in the longitudinal study group with joint cartilage damage, variation coefficients for CTX-II were 81% (between patients) and 64% (with in patient), monitored over I year. In a patient with septic arthritis, SF CTX-II increased at the onset of symptoms, and peaked 30-fold higher than the baseline. Concentrations of all biomarkers decreased with successful treatment.Conclusion. This is the first report to describe the release into SF of soluble molecular fragments specific for the degradation of mature, crosslinked, type II collagen (CII) in human OA and joint injury. The results provide strong evidence that the integrity of the CII network of cartilage is compromised soon after joint injury and in arthritis. This early degradation of CII may represent an important treatment target.