Stoop R, van der Kraan P M, Buma P, Hollander A P, Poole A R, van den Berg W B
Orthopaedic Research Laboratory, University Hospital Nijmegen, The Netherlands.
J Pathol. 1999 Jul;188(3):329-37. doi: 10.1002/(SICI)1096-9896(199907)188:3<329::AID-PATH371>3.0.CO;2-B.
Degradation of type II collagen is thought to be a key step in the destruction of articular cartilage in patients with rheumatoid arthritis or osteoarthritis. The aim of this study was to investigate whether type II collagen degradation is associated with cartilage destruction. Type II collagen degradation was studied in two murine arthritis models, zymosan-induced arthritis (ZIA), which develops reversible articular cartilage damage based on proteoglycan analysis, and antigen-induced arthritis (AIA), in which there is irreversible damage to the cartilage. Type II collagen degradation was assayed immunohistochemically using the COL2-3/4m antibody which recognizes denatured type II collagen, such as is produced by collagenase cleavage. In both models, degradation of type II collagen was observed in the non-calcified articular cartilage of arthritic but not of control knees. In the patella-femoral compartment, collagen denaturation started to increase on day 3 (ZIA) and day 7 (AIA) and remained high on day 14. In contrast, in the tibia-femoral compartment, type II collagen breakdown was not increased before 14 days in either model. By 28 days, collagen denaturation was strongly reduced in the patella-femoral compartment in the ZIA model, but persisted in the tibia-femoral compartment in both models. In conclusion, increased type II collagen degradation was found in articular cartilage of both ZIA and AIA animals. Since ZIA does not develop irreversible cartilage destruction, this indicates that cartilage may have the ability to withstand a limited degree of type II collagen degradation without developing irreversible damage.
II型胶原蛋白的降解被认为是类风湿性关节炎或骨关节炎患者关节软骨破坏的关键步骤。本研究的目的是调查II型胶原蛋白降解是否与软骨破坏有关。在两种小鼠关节炎模型中研究了II型胶原蛋白降解，即酵母聚糖诱导的关节炎（ZIA），基于蛋白聚糖分析，该模型会产生可逆的关节软骨损伤；以及抗原诱导的关节炎（AIA），该模型中软骨会出现不可逆损伤。使用识别变性II型胶原蛋白（如胶原酶切割产生的）的COL2-3/4m抗体通过免疫组织化学方法检测II型胶原蛋白降解。在两种模型中，均在患有关节炎的膝关节而非对照膝关节的非钙化关节软骨中观察到II型胶原蛋白的降解。在髌股关节腔，胶原变性在第3天（ZIA）和第7天（AIA）开始增加，并在第14天保持高水平。相比之下，在胫股关节腔，在两种模型中14天之前II型胶原蛋白的分解均未增加。到28天时，ZIA模型中髌股关节腔的胶原变性大幅降低，但在两种模型的胫股关节腔中仍持续存在。总之，在ZIA和AIA动物的关节软骨中均发现II型胶原蛋白降解增加。由于ZIA不会发展为不可逆的软骨破坏，这表明软骨可能有能力承受一定程度的II型胶原蛋白降解而不发生不可逆损伤。
