滑液中润滑分子的降解会改变软骨细胞对剪切应变的敏感性。

IF 2.1 3区 医学 Q2 ORTHOPEDICS
Steven Ayala, Salman O. Matan, Michelle L. Delco, Lisa A. Fortier, Itai Cohen, Lawrence J. Bonassar
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引用次数: 0

摘要

关节通过软骨组织和滑液的共同作用,形成低摩擦接触面,从而促进运动并将负荷传递到下层骨骼。软骨和周围关节囊受到的外伤会导致软骨细胞和滑膜分泌促炎细胞因子,引发软骨基质破坏,并损害滑液润滑关节的能力。一旦这些炎症过程变成慢性,创伤后骨关节炎(PTOA)就会开始发展。然而,滑液的负面改变导致 PTOA 发病的确切机制尚未完全明了。我们假设,去除滑液中的润滑大分子会改变受伤软骨中机械负荷与随后软骨细胞行为之间的关系。为了验证这一假设,我们采用了一种 PTOA 的体外模型,即让软骨外植体在健康滑液、磷酸盐缓冲盐水 (PBS)、透明质酸酶处理过的滑液或胰蛋白酶处理过的滑液的润滑浴中受到单次快速撞击,然后持续铰接。这些处理方法会降解滑膜液具有润滑特性的主要大分子:透明质酸和润滑蛋白。然后将外植体一分为二并进行荧光染色,以评估整体和深度依赖性细胞死亡、caspase 活性和线粒体去极化。通过共聚焦弹性成像技术检测外植体,以确定每种润滑剂产生的局部剪切应变曲线。这些结果表明,降解滑液中的透明质酸或润滑素会显著增加中间区软骨细胞的损伤和剪切应变加载幅度,同时也会改变软骨细胞对加载的敏感性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Degradation of lubricating molecules in synovial fluid alters chondrocyte sensitivity to shear strain

Articular joints facilitate motion and transfer loads to underlying bone through a combination of cartilage tissue and synovial fluid, which together generate a low-friction contact surface. Traumatic injury delivered to cartilage and the surrounding joint capsule causes secretion of proinflammatory cytokines by chondrocytes and the synovium, triggering cartilage matrix breakdown and impairing the ability of synovial fluid to lubricate the joint. Once these inflammatory processes become chronic, posttraumatic osteoarthritis (PTOA) development begins. However, the exact mechanism by which negative alterations to synovial fluid leads to PTOA pathogenesis is not fully understood. We hypothesize that removing the lubricating macromolecules from synovial fluid alters the relationship between mechanical loads and subsequent chondrocyte behavior in injured cartilage. To test this hypothesis, we utilized an ex vivo model of PTOA that involves subjecting cartilage explants to a single rapid impact followed by continuous articulation within a lubricating bath of either healthy synovial fluid, phosphate-buffered saline (PBS), synovial fluid treated with hyaluronidase, or synovial fluid treated with trypsin. These treatments degrade the main macromolecules attributed with providing synovial fluid with its lubricating properties; hyaluronic acid and lubricin. Explants were then bisected and fluorescently stained to assess global and depth-dependent cell death, caspase activity, and mitochondrial depolarization. Explants were tested via confocal elastography to determine the local shear strain profile generated in each lubricant. These results show that degrading hyaluronic acid or lubricin in synovial fluid significantly increases middle zone chondrocyte damage and shear strain loading magnitudes, while also altering chondrocyte sensitivity to loading.

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来源期刊
Journal of Orthopaedic Research®
Journal of Orthopaedic Research® 医学-整形外科
CiteScore
6.10
自引率
3.60%
发文量
261
审稿时长
3-6 weeks
期刊介绍: The Journal of Orthopaedic Research is the forum for the rapid publication of high quality reports of new information on the full spectrum of orthopaedic research, including life sciences, engineering, translational, and clinical studies.
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