Warmink K, Rios J L, van Valkengoed D R, Vinod P, Korthagen N M, Weinans H
Department of Orthopedics, University Medical Center Utrecht (UMCU), Utrecht, Netherlands.
Department of Equine Sciences, Utrecht University, Utrecht, Netherlands.
Front Physiol. 2023 Jul 13;14:1211972. doi: 10.3389/fphys.2023.1211972. eCollection 2023.
Obesogenic diets aggravate osteoarthritis (OA) by inducing low-grade systemic inflammation, and diet composition may affect OA severity. Here, we investigated the effect of diet on joint damage and inflammation in an OA rat model. Wistar-Han rats ( = 24) were fed a chow, a high-fat (HF) diet, or a high-fat/high-sucrose (HFS) for 24 weeks. OA was induced unilaterally 12 weeks after the diet onset by groove surgery, and compared to sham surgery or no surgical intervention (contralateral limb). Knee OA severity was determined by OARSI histopathology scoring system. At several timepoints monocyte populations were measured using flow cytometry, and joint macrophage response was determined via CD68 immunohistochemistry staining. Groove surgery combined with HF or HFS diet resulted in higher OARSI scores, and both HF and HFS diet showed increased circulating intermediate monocytes compared to chow fed rats. Additionally, in the HFS group, minimal damage by sham surgery resulted in an increased OARSI score. HFS diet resulted in the largest metabolic dysregulation, synovial inflammation and increased CD68 staining in tibia epiphysis bone marrow. Obesogenic diets resulted in aggravated OA development, even with very minimal joint damage when combined with the sucrose/fat-rich diet. We hypothesize that diet-induced low-grade inflammation primes monocytes and macrophages in the blood, bone marrow, and synovium, resulting in joint damage when triggered by groove OA inducing surgery. When the metabolic dysregulation is larger, as observed here for the HFS diet, the surgical trigger required to induce joint damage may be smaller, or even redundant.
致肥胖饮食通过引发低度全身炎症加重骨关节炎（OA），且饮食组成可能影响OA的严重程度。在此，我们研究了饮食对OA大鼠模型关节损伤和炎症的影响。将24只Wistar-Han大鼠分为三组，分别给予普通饲料、高脂（HF）饮食或高脂/高糖（HFS）饮食，持续24周。在饮食开始12周后，通过凹槽手术单侧诱导OA，并与假手术或无手术干预（对侧肢体）进行比较。采用OARSI组织病理学评分系统确定膝关节OA的严重程度。在几个时间点，使用流式细胞术测量单核细胞群体，并通过CD68免疫组织化学染色确定关节巨噬细胞反应。凹槽手术联合HF或HFS饮食导致OARSI评分更高，与喂食普通饲料的大鼠相比，HF和HFS饮食组的循环中间单核细胞均增加。此外，在HFS组中，假手术造成的轻微损伤导致OARSI评分增加。HFS饮食导致最大程度的代谢失调、滑膜炎症以及胫骨骨骺骨髓中CD68染色增加。致肥胖饮食导致OA病情加重，即使在与富含蔗糖/脂肪的饮食联合时关节损伤非常轻微。我们推测，饮食诱导的低度炎症使血液、骨髓和滑膜中的单核细胞和巨噬细胞致敏，在由凹槽OA诱导手术触发时导致关节损伤。当代谢失调更严重时，如此处观察到的HFS饮食，诱导关节损伤所需的手术触发因素可能更小，甚至是多余的。
