Structural changes in the collagen network of joint tissues in late stages of murine OA.
Structural changes in the collagen network of joint tissues in late stages of murine OA.
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小鼠 OA 晚期关节组织胶原蛋白网络的结构变化。
DOI：
10.1038/s41598-022-13062-y
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发表时间：
2022-06-01
影响因子：
4.6
通讯作者：
中科院分区：
文献类型：
--
作者：
骨关节炎（OA）是最常见的退行性关节疾病，导致关节疼痛、运动障碍和结构改变。由于关节组织抵抗应激的能力主要是由细胞外基质中的纤维状胶原赋予的，因此胶原纤维的组成和结构的变化有助于OA关节的病理重塑，包括软骨退变、软骨下骨（SCB）硬化和半月板损伤。利用建立的C57BL/6J小鼠内侧半月板失稳（DMM） OA模型，采用二次谐波显微镜和免疫荧光染色等互补技术，对关节软骨、软骨下骨和半月板中胶原纤维的含量和结构进行了全面分析。我们发现，OA小鼠暴露于机械应力增加的区域，通常最靠近损伤部位，胶原纤维厚度增加，纤维形成失调，胶原I和II （Col I和Col II）表达的组织特异性变化。在软骨中，OA与所有区域Col II表达降低有关，并与前、后区域Col I表达升高有关。各区域Col I纤维厚度均增加，中心区域组织疏松。在OA小鼠的浅表SCB中，所有区域的Col I表达和纤维厚度均增加；除了Col I纤维厚度增加外，在软骨下骨的较深区域未发现任何变化。在半月板中，OA导致前半月板血管区和无血管区Col I和Col II表达增加，这些区域Col I纤维厚度增加。类似的变化仅在后半月板血管区观察到。我们的研究结果首次对骨关节炎细胞外基质的微结构变化提供了全面的见解，并为研究靶向胶原改变的治疗方法作为阻止骨关节炎进展的手段提供了指导。
Osteoarthritis (OA) is the most prevalent degenerative joint disease, resulting in joint pain, impaired movement, and structural changes. As the ability of joint tissue to resist stress is mainly imparted by fibrillar collagens in the extracellular matrix, changes in the composition and structure of collagen fibers contribute to the pathological remodeling observed in OA joints that includes cartilage degeneration, subchondral bone (SCB) sclerosis, and meniscal damage. Using the established OA model of destabilization of the medial meniscus (DMM) in C57BL/6J mice, we performed a comprehensive analysis of the content and structure of collagen fibers in the articular cartilage, subchondral bone, and menisci using complementary techniques, which included second harmonic generation microscopy and immunofluorescence staining. We found that regions exposed to increased mechanical stress in OA mice, typically closest to the site of injury, had increased collagen fiber thickness, dysregulated fiber formation, and tissue specific changes in collagen I and II (Col I and Col II) expression. In cartilage, OA was associated with decreased Col II expression in all regions, and increased Col I expression in the anterior and posterior regions. Col I fiber thickness was increased in all regions with disorganization in the center region. In the superficial SCB, all regions exhibited increased Col I expression and fiber thickness in OA mice; no changes were detected in the deeper regions of the subchondral bone except for increased Col I fiber thickness. In the menisci, OA led to increased Col I and Col II expression in the vascular and avascular regions of the anterior meniscus with increased Col I fiber thickness in these regions. Similar changes were observed only in the vascular region of the posterior meniscus. Our findings provide, for the first time, comprehensive insights into the microarchitectural changes of extracellular matrix in OA and serve as guidelines for studies investigating therapies that target collagenous changes as means to impede the progression of osteoarthritis.
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影响因子：
12.7
作者：
Findlay, David M.;Kuliwaba, Julia S.
通讯作者：
Kuliwaba, Julia S.
影响因子：
2.2
作者：
Lajeunesse, D;Massicotte, F;Martel-Pelletier, J
通讯作者：
Martel-Pelletier, J
体内 ACL 损伤后，异常机械负荷通过加速半月板肥大和矿化而诱导软骨退化
DOI：
10.1177/0363546515621285
发表时间：
2016-03
期刊：
The American journal of sports medicine
影响因子：
--
作者：
Du G;Zhan H;Ding D;Wang S;Wei X;Wei F;Zhang J;Bilgen B;Reginato AM;Fleming BC;Deng J;Wei L
通讯作者：
Wei L
影响因子：
17.1
作者：
Carlson, Elijah L.;Karuppagounder, Vengadeshprabhu;Kamal, Fadia
通讯作者：
Kamal, Fadia
影响因子：
3.2
作者：
Lattouf, Raed;Younes, Ronald;Changotade, Sylvie
通讯作者：
Changotade, Sylvie