Weber Patrick, Bevc Kajetana, Fercher David, Kauppinen Sami, Zhang Shipin, Asadikorayem Maryam, Marin Lucia Baixauli, Zhang Tanqi, Frondelius Tuomas, Salzmann Gian, Bruhin Valentino, Hax Jakob, Barreto Gonçalo, Finnilä Mikko A J, Zenobi-Wong Marcy
Tissue Engineering + Biofabrication Laboratory, Department of Health Sciences and Technology, ETH Zürich, Otto-Stern-Weg 7, 8093 Zurich, Switzerland.
Research Unit of Health Sciences and Technology, University of Oulu, Aapistie 5A, 90220, Oulu, Finland.
Osteoarthr Cartil Open. 2024 Oct 24;6(4):100539. doi: 10.1016/j.ocarto.2024.100539. eCollection 2024 Dec.
To characterize inflammatory and mechanical changes in the collagenase-induced OA (CIOA) model in rats.
Skeletally mature, 6-month-old Wistar rats received unilateral intraarticular injections of saline, 500 U or 1000 U of collagenase on days 0 and 2 of the study. Joint tissues were harvested on either day 4 or 70 to evaluate the acute and long-term changes. Blood biomarkers, gait asymmetry and mechanical hyperalgesia were assessed repeatedly up until day 70.
The intraarticular injection of collagenase triggered an increase in cartilage degeneration and bone resorption over time, particularly for 1000 U. Similarly, mild synovitis was observed on day 70 with an increased number of synovial lining cells, increased fibrosis, and infiltration of peripheral macrophages. Mechanistically, these findings were linked to a dose-related mechanical weakening of the anterior cruciate ligament (ACL), which caused persistent joint destabilization throughout the study. Furthermore, the collagenase injection triggered acute inflammation and swelling of the synovium on day 4 and an acute systemic inflammatory response with increased cytokine and peripheral blood immune cell levels. While mild synovitis persisted until day 70, the systemic inflammatory response returned to control levels after 8 days. Similarly, the observed acute changes in gait and mechanical hyperalgesia also returned to baseline after 21 days.
By evaluating inflammatory and mechanical factors at different doses and timepoints, our characterization enables a more targeted study design and increases the clinical relevance of future studies involving the CIOA model.
描述大鼠胶原酶诱导性骨关节炎（CIOA）模型中的炎症和力学变化。
在研究的第0天和第2天，对骨骼成熟的6月龄Wistar大鼠单侧关节内注射生理盐水、500 U或1000 U胶原酶。在第4天或第70天采集关节组织，以评估急性和长期变化。在第70天之前反复评估血液生物标志物、步态不对称和机械性痛觉过敏。
随着时间的推移，关节内注射胶原酶会引发软骨退变和骨吸收增加，尤其是1000 U剂量组。同样，在第70天观察到轻度滑膜炎，滑膜衬里细胞数量增加、纤维化增加以及外周巨噬细胞浸润。从机制上讲，这些发现与前交叉韧带（ACL）的剂量相关力学减弱有关，这在整个研究过程中导致了持续的关节不稳定。此外，胶原酶注射在第4天引发了滑膜的急性炎症和肿胀以及急性全身炎症反应，细胞因子和外周血免疫细胞水平升高。虽然轻度滑膜炎持续到第70天，但全身炎症反应在8天后恢复到对照水平。同样，观察到的步态和机械性痛觉过敏的急性变化在21天后也恢复到基线水平。
通过在不同剂量和时间点评估炎症和力学因素，我们的特征描述能够实现更具针对性的研究设计，并提高未来涉及CIOA模型研究的临床相关性。
