Joint instability causes catabolic enzyme production in chondrocytes prior to synovial cells in novel non-invasive ACL ruptured mouse model
Joint instability causes catabolic enzyme production in chondrocytes prior to synovial cells in novel non-invasive ACL ruptured mouse model
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DOI：
10.1016/j.joca.2022.12.004
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发表时间：
2023-04-28
影响因子：
7
通讯作者：
Kokubun，T.
中科院分区：
文献类型：
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作者：
Takahata，K.;Arakawa，K.;Kokubun，T.
前交叉韧带（ACL）缺陷模型有助于阐明膝关节骨关节炎（OA）的机制;然而，传统的ACL损伤模型可能包括并发发病因素，如对软骨和软骨下骨的直接压缩应力。在这项研究中，我们建立了一种新的非侵入性ACL-破裂的小鼠模型，没有并发injuries.DesignWe诱导ACL-破裂非侵入性12周龄的C57 BL/6雄性小鼠和评估组织学，宏观和形态学分析在0天的OA进展和关节不稳定之间的关系。接下来，我们创建了ACL-R、受控异常胫骨平移（CATT）和假手术组。然后，关节稳定性和OA的病理生理学进行了分析，在2，4，8 wk.ResultsNo关节内损伤，除了ACL断裂，观察在ACL-R模型。与假手术组（P< 0.001，95%CI [-1.509至-0.966]）和CATT组（P< 0.001，95%CI [-0.841至-0.298]）相比，ACL-R小鼠在8周时增加了胫骨前移位。ACL-R组的所有小鼠均引起软骨退变。8周时，ACL-R组的软骨退变程度高于CATT组（P= 0.006）。术后4周ACL-R组软骨细胞MMP-3阳性细胞率较CATT组增加（P= 0.043; 95% CI [-28.32至0.364]），而滑膜细胞的增加在8周时（P= 0.031; 95%CI [-23.398 to-1.021]）.结论我们成功建立了无关节内损伤的无创ACL-R模型。我们的模型显示，在膝关节OA发病时，软骨细胞可能先于滑膜细胞对异常机械应力作出反应。
ObjectiveThe Anterior Cruciate Ligament (ACL)-deficient model helps to clarify the mechanism of knee osteoarthritis (OA); however, the conventional ACL injury model could have included concurrent onset factors such as direct compression stress to cartilage and subchondral bone. In this study, we established a novel Non-invasive ACL-Ruptured mouse model without concurrent injuries and elucidated the relationship between OA progression and joint instability.DesignWe induced the ACL-Rupture non-invasively in twelve-week-old C57BL/6 male mice and evaluated histological, macroscopical, and morphological analysis at 0 days. Next, we created the ACL-R, controlled abnormal tibial translation (CATT), and Sham groups. Then, the joint stability and OA pathophysiology were analyzed at 2, 4, and 8 weeks.ResultsNo intra-articular injuries, except for ACL rupture, were observed in the ACL-R model. ACL-R mice increased anterior tibial displacement compared to the Sham group (P< 0.001, 95% CI [−1.509 to −0.966]) and CATT group (P< 0.001, 95% CI [−0.841 to −0.298]) at 8 weeks. All mice in the ACL-R group caused cartilage degeneration. The degree of cartilage degeneration in the ACL-R group was higher than in the CATT group (P= 0.006) at 8 weeks. The MMP-3-positive cell rate of chondrocytes increased in the ACL-R group than CATT group from 4 weeks (P= 0.043; 95% CI [−28.32 to −0.364]) while that of synovial cells increased at 8 weeks (P= 0.031; 95% CI [−23.398 to −1.021]).ConclusionWe successfully established a Non-invasive ACL-R model without intra-articular damage. Our model revealed that chondrocytes might react to abnormal mechanical stress prior to synovial cells while the knee OA onset.