Vinardell T, Dejica V, Poole A R, Mort J S, Richard H, Laverty S
Département des sciences cliniques, Faculté de Médecine Vétérinaire, Université de Montréal, St. Hyacinthe, Québec, Canada.
Osteoarthritis Cartilage. 2009 Mar;17(3):375-83. doi: 10.1016/j.joca.2008.07.017. Epub 2008 Sep 21.
The mechanisms leading to degeneration of articular cartilage in osteoarthritis (OA) are complex and not yet fully understood. Cathepsin K (CK) is a cysteine protease which can also cleave the triple helix of type II collagen. This exposes a neoepitope that can now be identified by specific antibodies. The aim of this study was to obtain evidence suggesting a role for CK in naturally occurring equine OA in both lesional and peri-lesional regions.
Articular cartilages (n=12 horses; 5 healthy, 7 OA) were harvested from animals postmortem. A gross macroscopic examination, histologic (Safranin O-Fast Green and Picrosirius red staining) and immunohistochemical evaluation were performed. Samples were divided into normal appearing cartilage, peri-lesional and lesional cartilage. Cartilage degradation in the samples was graded histologically and immunohistochemically. CK and possible CK cleavage were detected immunohistochemically with specific anti-protein and anti-neoepitope antibodies, respectively. A comparison of CK neoepitope (C2K) production with the collagenase-generated neoepitope produced by matrix metalloproteinases (MMP)-1, 8 and 13 (C2C) was also assessed immunohistochemically.
CK and CK cleavage were significantly more abundant in OA cartilage (both peri-lesional and lesional) when compared to remote cartilage within the sample joint or cartilage from healthy joints. The immunohistochemical pattern observed for CK degradation (C2K) was similar to that of collagenase degradation (C2C). Macroscopic cartilage changes and histologic findings were significantly correlated with immunohistochemistry results.
The data generated suggests that CK may be involved in cartilage collagen degradation in naturally occurring osteoarthritis.
骨关节炎（OA）中导致关节软骨退变的机制复杂，尚未完全明确。组织蛋白酶K（CK）是一种半胱氨酸蛋白酶，它也能切割Ⅱ型胶原的三股螺旋结构。这会暴露出一个新表位，现在可以通过特异性抗体识别。本研究的目的是获得证据，表明CK在自然发生的马OA的病变区和病变周围区域发挥作用。
从死后的动物身上获取关节软骨（n = 12匹马；5匹健康，7匹OA）。进行大体宏观检查、组织学（番红O-固绿和天狼星红染色）和免疫组织化学评估。样本分为外观正常的软骨、病变周围软骨和病变软骨。对样本中的软骨退变进行组织学和免疫组织化学分级。分别用特异性抗蛋白抗体和抗新表位抗体免疫组织化学检测CK和可能的CK切割情况。还通过免疫组织化学评估了CK新表位（C2K）的产生与基质金属蛋白酶（MMP）-1、8和13产生的胶原酶生成新表位（C2C）的比较。
与样本关节内的远端软骨或健康关节的软骨相比，OA软骨（病变周围和病变区）中的CK和CK切割明显更丰富。观察到的CK降解（C2K）的免疫组织化学模式与胶原酶降解（C2C）相似。宏观软骨变化和组织学结果与免疫组织化学结果显著相关。
所产生的数据表明，CK可能参与自然发生的骨关节炎中软骨胶原的降解。
