Osteoarthritis Research, Merck KGaA, Darmstadt, Germany.
Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Chaterhouse Square, London, EC1M 6BQ, UK.
Arthritis Res Ther. 2021 Apr 14;23(1):113. doi: 10.1186/s13075-021-02502-1.
Osteoarthritis (OA) is a disease of the whole joint, with articular cartilage breakdown as a major characteristic. Inflammatory mediators, proteases, and oxidants produced by chondrocytes are known to be responsible for driving cartilage degradation. Nevertheless, the early pathogenic events are still unclear. To investigate this, we employed an antibody that is specific to oxidative post-translationally modified collagen type II (anti-oxPTM-CII) to detect early cartilage pathogenic changes in two rat models of OA.
The animals underwent surgery for destabilization of the medial meniscus (DMM) and were sacrificed after 3, 5, 7, 14, and 28 days. Alternatively, anterior cruciate ligament transection with partial meniscectomy (ACLT+pMx) was performed and animals were sacrificed after 1, 3, 5, 7, and 14 days. Joints were stained with toluidine blue and saffron du Gatinais for histological scoring, anti-oxPTM-CII, and anti-collagen type X antibodies (anti-CX).
We observed positive oxPTM-CII staining as early as 1 or 3 days after ACLT+pMx or DMM surgeries, respectively, before overt cartilage lesions were visible. oxPTM-CII was located mostly in the deep zone of the medial tibial cartilage, in the pericellular and territorial matrix of hypertrophic chondrocytes, and co-localized with CX staining. Staining was weak or absent for the lateral compartment or the contralateral knees except at later time points.
The results demonstrate that oxidant production and chondrocyte hypertrophy occur very early in the onset of OA, possibly initiating the pathogenic events of OA. We propose to use anti-oxPTM-CII as an early biomarker for OA ahead of radiographic changes.
骨关节炎（OA）是一种全身性关节疾病，以关节软骨破坏为主要特征。已知软骨细胞产生的炎症介质、蛋白酶和氧化剂负责驱动软骨降解。然而，早期的发病事件仍不清楚。为了研究这一点，我们使用了一种针对氧化后翻译修饰的 II 型胶原（anti-oxPTM-CII）的抗体来检测两种 OA 大鼠模型中的早期软骨发病变化。
动物接受内侧半月板不稳定（DMM）手术，并在 3、5、7、14 和 28 天后处死。或者进行前交叉韧带切断伴部分半月板切除术（ACLT+pMx），并在 1、3、5、7 和 14 天后处死动物。关节用甲苯胺蓝和藏红花 du Gatinais 染色进行组织学评分、抗 oxPTM-CII 和抗型胶原 X 抗体（抗-CX）染色。
我们观察到在 ACLT+pMx 或 DMM 手术后 1 或 3 天，即在明显的软骨病变出现之前，就出现了阳性的 oxPTM-CII 染色。oxPTM-CII 主要位于内侧胫骨软骨的深层区域，位于肥大软骨细胞的细胞周和区域基质中，与 CX 染色共定位。除了在后期时间点外，外侧间室或对侧膝关节的染色较弱或不存在。
这些结果表明，氧化剂产生和软骨细胞肥大发生在 OA 发病的早期，可能引发 OA 的发病事件。我们建议在出现放射学变化之前，使用抗 oxPTM-CII 作为 OA 的早期生物标志物。
