Sibley School of Mechanical and Aerospace Engineering, Cornell University, Ithaca, New York.
Meinig School of Biomedical Engineering, Cornell University, Ithaca, New York.
J Orthop Res. 2021 May;39(5):1007-1016. doi: 10.1002/jor.24799. Epub 2020 Jul 17.
Osteoarthritis is increasingly viewed as a heterogeneous disease with multiple phenotypic subgroups. Obesity enhances joint degeneration in mouse models of posttraumatic osteoarthritis (PTOA). Most models of PTOA involve damage to surrounding tissues caused by surgery/fracture; it is unclear if obesity enhances cartilage degeneration in the absence of surgery/fracture. We used a nonsurgical animal model of load-induced PTOA to determine the effect of obesity on cartilage degeneration 2 weeks after loading. Cartilage degeneration was caused by a single bout of cyclic tibial loading at either a high or moderate load magnitude in adult male mice with severe obesity (C57Bl6/J + high-fat diet), mild obesity (toll-like receptor 5 deficient mouse [TLR5KO]), or normal adiposity (C57Bl6/J mice + normal diet and TLR5KO mice in which obesity was prevented by manipulation of the gut microbiome). Two weeks after loading, cartilage degeneration occurred in limbs loaded at a high magnitude, as determined by OARSI scores (P < .001). However, the severity of cartilage damage did not differ among groups. Osteophyte width and synovitis of loaded limbs did not differ among groups. Furthermore, obesity did not enhance cartilage damage in limbs evaluated 6 weeks after loading. Constituents of the gut microbiota differed among groups. Our findings suggest that, in the absence of surgery/fracture, obesity may not influence cartilage loss after a single mechanical insult, suggesting that either damage to surrounding tissues or repeated mechanical insult is necessary for obesity to influence cartilage degeneration. These findings further illustrate heterogeneity in PTOA phenotypes and complex interactions between mechanical/metabolic factors in cartilage loss.
骨关节炎越来越被视为一种具有多种表型亚组的异质性疾病。肥胖会增强小鼠创伤后骨关节炎（PTOA）模型中的关节退化。大多数 PTOA 模型都涉及手术/骨折引起的周围组织损伤；目前尚不清楚肥胖是否会在没有手术/骨折的情况下加剧软骨退化。我们使用一种非手术性的负荷诱导 PTOA 动物模型，以确定肥胖对负荷后 2 周软骨退化的影响。在严重肥胖（C57Bl6/J + 高脂肪饮食）、轻度肥胖（Toll 样受体 5 缺陷型小鼠 [TLR5KO]）或正常肥胖（C57Bl6/J 小鼠+正常饮食和 TLR5KO 小鼠，其肥胖通过肠道微生物组的操作来预防）的成年雄性小鼠中，单次循环胫骨负荷会导致软骨退化。在高负荷或中负荷下，软骨退化是由单次负荷引起的，通过 OARSI 评分（P < 0.001）确定。然而，各组之间的软骨损伤严重程度没有差异。各组之间负荷肢体的骨赘宽度和滑膜炎没有差异。此外，肥胖并未增加负荷后 6 周时肢体的软骨损伤。各组之间的肠道微生物群组成不同。我们的研究结果表明，在没有手术/骨折的情况下，肥胖可能不会影响单次机械损伤后的软骨丢失，这表明周围组织的损伤或反复的机械损伤是肥胖影响软骨退化所必需的。这些发现进一步说明了 PTOA 表型的异质性以及机械/代谢因素在软骨丢失中的复杂相互作用。
