Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis.
Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis.
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DOI：
10.1371/journal.pone.0183693
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Prasadam I
中科院分区：
文献类型：
--
作者：
Sun AR;Panchal SK;Friis T;Sekar S;Crawford R;Brown L;Xiao Y;Prasadam I
流行病学和实验研究已经确定肥胖是骨关节炎（OA）的一个重要危险因素，然而，这种联系的机制在很大程度上仍然未知。在这里，我们研究了代谢性oa的局部炎症反应。Wistar大鼠分别饲喂对照日粮（CD）和高碳水化合物、高脂肪日粮（HCHF），为期8周和16周。安乐死后，对膝关节进行检查，以评估关节软骨的变化和滑膜的炎症。进一步进行免疫组化以确定滑膜的巨噬细胞极化状态。此外，将CD和HCHF滑膜液与骨髓源性巨噬细胞共培养，以评估滑膜液炎症对巨噬细胞极化的影响。我们的研究表明，高碳水化合物，高脂肪（HCHF）饮食引起的肥胖与大鼠滑膜自发和局部炎症有关，甚至在软骨降解之前。随后滑膜炎加重，滑膜内巨噬细胞浸润增多，促炎M1巨噬细胞显著升高。此外，与肥胖大鼠膝关节滑液培养的骨髓源性巨噬细胞表现出促炎M1巨噬细胞表型。我们的研究表明，肥胖和滑膜组织局部动态免疫反应之间有很强的联系。此外，我们还发现滑膜巨噬细胞在HCHF饮食引起的炎症中起着至关重要的作用。因此，未来针对滑膜巨噬细胞表型的治疗策略可能是打破肥胖与OA之间联系的关键。
Epidemiological and experimental studies have established obesity to be an important risk factor for osteoarthritis (OA), however, the mechanisms underlying this link remains largely unknown. Here, we studied local inflammatory responses in metabolic-OA. Wistar rats were fed with control diet (CD) and high-carbohydrate, high-fat diet (HCHF) for period of 8 and 16 weeks. After euthanasia, the knees were examined to assess the articular cartilage changes and inflammation in synovial membrane. Further IHC was conducted to determine the macrophage-polarization status of the synovium. In addition, CD and HCHF synovial fluid was co-cultured with bone marrow-derived macrophages to assess the effect of synovial fluid inflammation on macrophage polarisation. Our study showed that, obesity induced by a high-carbohydrate, high-fat (HCHF) diet is associated with spontaneous and local inflammation of the synovial membranes in rats even before the cartilage degradation. This was followed by increased synovitis and increased macrophage infiltration into the synovium and a predominant elevation of pro-inflammatory M1 macrophages. In addition, bone marrow derived macrophages, cultured with synovial fluid collected from the knees of obese rats exhibited a pro-inflammatory M1 macrophage phenotype. Our study demonstrate a strong association between obesity and a dynamic immune response locally within synovial tissues. Furthermore, we have also identified synovial resident macrophages to play a vital role in the inflammation caused by the HCHF diet. Therefore, future therapeutic strategies targeted at the synovial macrophage phenotype may be the key to break the link between obesity and OA.
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影响因子：
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