Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non-invasive murine model of post-traumatic osteoarthritis.
Inflammatory and degenerative phases resulting from anterior cruciate rupture in a non-invasive murine model of post-traumatic osteoarthritis.
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DOI：
10.1002/jor.23872
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发表时间：
2018-02-17
期刊：
影响因子：
--
通讯作者：
Blain EJ
中科院分区：
文献类型：
--
作者：
Gilbert SJ;Bonnet CS;Stadnik P;Duance VC;Mason DJ;Blain EJ
关节损伤是创伤后骨关节炎发展（PTOA）的主要风险因素。几种模拟人类PTOA的非侵入性小鼠模型研究了疾病发展的分子机制;没有一种模型表征了对这种急性创伤性损伤的炎症反应。我们的目的是在前交叉韧带（ACL）断裂诱导的PTOA体内非侵入性小鼠模型中表征早期炎症阶段和后期退行性成分。将12周龄C57 B16小鼠的右膝以30°偏置屈曲放置，并施加单次压缩载荷（12 N，1.4 mm/s）以诱导ACL断裂，对周围组织无明显损伤。在损伤后4小时和第3、14和21天采集组织;对侧左膝作为对照。进行组织学、免疫组织化学和基因分析以评价炎症和退行性变化。免疫组织化学显示，滑膜下浸润、骨赘形成和ACL周围炎症反应中成熟（F4/80阳性）和炎症（CD 11b阳性）巨噬细胞群的表达呈时间依赖性。在股骨软骨中检测到编码急性促炎标志物、诱导型一氧化氮合酶、白细胞介素6和白细胞介素17以及基质降解酶ADAMTS-4和MMP 3的基因上调，伴随着损伤后21天的广泛软骨损伤和骨重建。我们的非侵入性模型描述了疾病的病理学不同阶段，增加了我们对炎症发作、产生炎症介质的组织/细胞以及关节中早期分子变化的理解，从而定义了PTOA的早期表型。这些知识将指导适当的干预措施，以延迟或阻止关节损伤后的疾病进展。版权所有© 2018作者. Journal of Orthopathy Research®由Wiley Periodicals，Inc.出版。我代表矫形外科研究协会J Orthop Res 36：2118-2127，2018.
Joint injury is the predominant risk factor for post‐traumatic osteoarthritis development (PTOA). Several non‐invasive mouse models mimicking human PTOA investigate molecular mechanisms of disease development; none have characterized the inflammatory response to this acute traumatic injury. Our aim was to characterize the early inflammatory phase and later degenerative component in our in vivo non‐invasive murine model of PTOA induced by anterior cruciate ligament (ACL) rupture. Right knees of 12‐week‐old C57Bl6 mice were placed in flexion at a 30° offset position and subjected to a single compressive load (12N, 1.4 mm/s) to induce ACL rupture with no obvious damage to surrounding tissues. Tissue was harvested 4 h post‐injury and on days 3, 14, and 21; contralateral left knees served as controls. Histological, immunohistochemical, and gene analyzes were performed to evaluate inflammatory and degenerative changes. Immunohistochemistry revealed time‐dependent expression of mature (F4/80 positive) and inflammatory (CD11b positive) macrophage populations within the sub‐synovial infiltrate, developing osteophytes, and inflammation surrounding the ACL in response to injury. Up‐regulation of genes encoding acute pro‐inflammatory markers, inducible nitric oxide synthase, interleukin‐6 and interleukin‐17, and the matrix degrading enzymes, ADAMTS‐4 and MMP3 was detected in femoral cartilage, concomitant with extensive cartilage damage and bone remodelling over 21‐days post‐injury. Our non‐invasive model describes pathologically distinct phases of the disease, increasing our understanding of inflammatory episodes, the tissues/cells producing inflammatory mediators and the early molecular changes in the joint, thereby defining the early phenotype of PTOA. This knowledge will guide appropriate interventions to delay or arrest disease progression following joint injury. © 2018 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. on behalf of the Orthopaedic Research Society. J Orthop Res 36:2118–2127, 2018.
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