Kerr Geoffrey J, To Bethia, White Ian, Millecamps Magali, Beier Frank, Grol Matthew W, Stone Laura S, Séguin Cheryle A
Department of Physiology & Pharmacology, Schulich School of Medicine & Dentistry, Bone and Joint Institute, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.
Alan Edwards Centre for Research on Pain, Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.
Arthritis Res Ther. 2021 Mar 22;23(1):93. doi: 10.1186/s13075-021-02463-5.
Obesity is one of the largest modifiable risk factors for the development of musculoskeletal diseases, including intervertebral disc (IVD) degeneration and back pain. Despite the clinical association, no studies have directly assessed whether diet-induced obesity accelerates IVD degeneration, back pain, or investigated the biological mediators underlying this association. In this study, we examine the effects of chronic consumption of a high-fat or high-fat/high-sugar (western) diet on the IVD, knee joint, and pain-associated outcomes.
Male C57BL/6N mice were randomized into one of three diet groups (chow control; high-fat; high-fat, high-sugar western diet) at 10 weeks of age and remained on the diet for 12, 24, or 40 weeks. At endpoint, animals were assessed for behavioral indicators of pain, joint tissues were collected for histological and molecular analysis, serum was collected to assess for markers of systemic inflammation, and IBA-1, GFAP, and CGRP were measured in spinal cords by immunohistochemistry.
Animals fed obesogenic (high-fat or western) diets showed behavioral indicators of pain beginning at 12 weeks and persisting up to 40 weeks of diet consumption. Histological indicators of moderate joint degeneration were detected in the IVD and knee following 40 weeks on the experimental diets. Mice fed the obesogenic diets showed synovitis, increased intradiscal expression of inflammatory cytokines and circulating levels of MCP-1 compared to control. Linear regression modeling demonstrated that age and diet were both significant predictors of most pain-related behavioral outcomes, but not histopathological joint degeneration. Synovitis was associated with alterations in spontaneous activity.
Diet-induced obesity accelerates IVD degeneration and knee OA in mice; however, pain-related behaviors precede and are independent of histopathological structural damage. These findings contribute to understanding the source of obesity-related back pain and the contribution of structural IVD degeneration.
肥胖是肌肉骨骼疾病发生的最大可改变风险因素之一，包括椎间盘退变和背痛。尽管存在临床关联，但尚无研究直接评估饮食诱导的肥胖是否会加速椎间盘退变、背痛，或探究这种关联背后的生物学介质。在本研究中，我们研究了长期食用高脂或高脂/高糖（西式）饮食对椎间盘、膝关节及疼痛相关结局的影响。
10周龄雄性C57BL/6N小鼠被随机分为三个饮食组之一（普通饮食对照组；高脂饮食组；高脂、高糖西式饮食组），并持续喂食12、24或40周。在实验终点，评估动物的疼痛行为指标，收集关节组织进行组织学和分子分析，收集血清评估全身炎症标志物，并通过免疫组织化学法检测脊髓中的IBA-1、GFAP和CGRP。
喂食致肥胖（高脂或西式）饮食的动物在进食12周时开始出现疼痛行为指标，并持续至进食40周。在实验饮食40周后，在椎间盘和膝关节中检测到中度关节退变的组织学指标。与对照组相比，喂食致肥胖饮食的小鼠出现滑膜炎，椎间盘内炎性细胞因子表达增加，MCP-1循环水平升高。线性回归模型表明，年龄和饮食都是大多数疼痛相关行为结局的重要预测因素，但不是组织病理学关节退变的预测因素。滑膜炎与自发活动的改变有关。
饮食诱导的肥胖会加速小鼠的椎间盘退变和膝关节骨关节炎；然而，疼痛相关行为先于组织病理学结构损伤出现且与之无关。这些发现有助于理解肥胖相关背痛的来源以及椎间盘结构退变的作用。
