David Michael A, Smith Melanie K, Pilachowski Rachael N, White Avery T, Locke Ryan C, Price Christopher
Department of Biomedical Engineering, University of Delaware, 161 Colburn Lab, Newark, Delaware, 19716.
J Orthop Res. 2017 Mar;35(3):537-547. doi: 10.1002/jor.23443. Epub 2016 Oct 6.
Post-traumatic osteoarthritis (PTOA) is an accelerated form of osteoarthritic cartilage degeneration affecting approximately 20-50% of patients experiencing joint injury. Currently PTOA is incurable; to better understand the etiology of PTOA and to develop rational anti-osteoarthritic therapies, it is critical to understand the spatiotemporal initiation and the progression of PTOA. In this study, we employed semi-quantitative histological scoring and quantitative damage analysis to examine disease progression in the murine destabilization of the medial meniscus (DMM) model of PTOA from early (3 days) through late- (112 days) disease timepoints. We observed significant, progressive articular cartilage (AC) cellular, and structural changes in the medial compartments of injured joints as early as 3 days. Spatially within the joint, cartilage damage (erosions) were observed anteriorly at 84 days. Furthermore, a drastic loss in chondrocyte number (by 3 days), surface damage (at 7 days), and cartilage erosion (at 84 days) was found to co-localize to the specific region of the medial tibial plateau AC that experienced a change in meniscal coverage due to meniscal extrusion following DMM. Taken together, these results suggest that DMM-mediated extrusion of the medial meniscus leads to rapid, spatially dependent changes in AC cellularity and structure, and precipitates the focal degeneration of cartilage associated with PTOA. Importantly, this study suggests that joint instability injuries may trigger immediate (<3 days) processes within a small population of chondrocytes that directs the initiation and progression of PTOA, and that development of chondroprotective strategies for preventing and/or delaying PTOA-related cartilage degeneration are best targeted toward these immediately early processes following joint injury. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:537-547, 2017.
创伤后骨关节炎（PTOA）是骨关节炎性软骨退变的一种加速形式，影响约20%-50%的关节损伤患者。目前PTOA无法治愈；为了更好地理解PTOA的病因并开发合理的抗骨关节炎疗法，了解PTOA的时空起始和进展至关重要。在本研究中，我们采用半定量组织学评分和定量损伤分析，来检查PTOA小鼠内侧半月板不稳定（DMM）模型从疾病早期（3天）到晚期（112天）各时间点的疾病进展。我们观察到，早在3天时，受伤关节内侧间室的关节软骨（AC）就出现了显著的、渐进性的细胞和结构变化。在关节空间内，84天时在前方观察到软骨损伤（侵蚀）。此外，发现软骨细胞数量急剧减少（3天时）、表面损伤（7天时）和软骨侵蚀（84天时）共同定位于内侧胫骨平台AC的特定区域，该区域由于DMM后半月板挤出而经历了半月板覆盖的变化。综上所述，这些结果表明，DMM介导的内侧半月板挤出导致AC细胞数量和结构快速、空间依赖性变化，并促成了与PTOA相关的软骨局灶性退变。重要的是，本研究表明，关节不稳定损伤可能在一小部分软骨细胞内触发即时（<3天）过程，这些过程指导PTOA的起始和进展，并且开发用于预防和/或延迟PTOA相关软骨退变的软骨保护策略最好针对关节损伤后的这些即时早期过程。©2016骨科研究协会。由Wiley Periodicals, Inc.出版。《矫形外科学研究》35:537 - 547，2017年。
