de Jong Anja J, Klein-Wieringa Inge R, Andersen Stefan N, Kwekkeboom Joanneke C, Herb-van Toorn Linda, de Lange-Brokaar Badelog J E, van Delft Danny, Garcia John, Wei Wu, van der Heide Huub J L, Bastiaansen-Jenniskens Yvonne M, van Osch Gerjo J V M, Zuurmond Annemarie M, Stojanovic-Susulic Vedrana, Nelissen Rob G H H, Toes René E M, Kloppenburg Margreet, Ioan-Facsinay Andreea
Department of Rheumatology, Leiden University Medical Centre, C1-R, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
Department of Orthopaedics, Leiden University Medical Center, Leiden, The Netherlands.
Arthritis Res Ther. 2017 Aug 11;19(1):186. doi: 10.1186/s13075-017-1395-9.
Obesity is associated with the development and progression of osteoarthritis (OA). Although the infrapatellar fat pad (IFP) could be involved in this association, due to its intracapsular localization in the knee joint, there is currently little known about the effect of obesity on the IFP. Therefore, we investigated cellular and molecular body mass index (BMI)-related features in the IFP of OA patients.
Patients with knee OA (N = 155, 68% women, mean age 65 years, mean (SD) BMI 29.9 kg/m2 (5.7)) were recruited: IFP volume was determined by magnetic resonance imaging in 79 patients with knee OA, while IFPs and subcutaneous adipose tissue (SCAT) were obtained from 106 patients undergoing arthroplasty. Crown-like structures (CLS) were determined using immunohistochemical analysis. Adipocyte size was determined by light microscopy and histological analysis. Stromal vascular fraction (SVF) cells were characterized by flow cytometry.
IFP volume (mean (SD) 23.6 (5.4) mm) was associated with height, but not with BMI or other obesity-related features. Likewise, volume and size of IFP adipocytes (mean 271 pl, mean 1933 μm) was not correlated with BMI. Few CLS were observed in the IFP, with no differences between overweight/obese and lean individuals. Moreover, high BMI was not associated with higher SVF immune cell numbers in the IFP, nor with changes in their phenotype. No BMI-associated molecular differences were observed, besides an increase in TNFα expression with high BMI. Macrophages in the IFP were mostly pro-inflammatory, producing IL-6 and TNFα, but little IL-10. Interestingly, however, CD206 and CD163 were associated with an anti-inflammatory phenotype, were the most abundantly expressed surface markers on macrophages (81% and 41%, respectively) and CD163 macrophages had a more activated and pro-inflammatory phenotype than their CD163 counterparts.
BMI-related features usually observed in SCAT and visceral adipose tissue could not be detected in the IFP of OA patients, a fat depot implicated in OA pathogenesis.
肥胖与骨关节炎（OA）的发生和发展相关。尽管髌下脂肪垫（IFP）可能参与了这种关联，但由于其位于膝关节囊内，目前关于肥胖对IFP的影响知之甚少。因此，我们研究了OA患者IFP中与细胞和分子体重指数（BMI）相关的特征。
招募膝OA患者（N = 155，68%为女性，平均年龄65岁，平均（标准差）BMI为29.9 kg/m²（5.7））：79例膝OA患者通过磁共振成像测定IFP体积，106例行关节置换术的患者获取IFP和皮下脂肪组织（SCAT）。采用免疫组织化学分析确定冠状结构（CLS）。通过光学显微镜和组织学分析确定脂肪细胞大小。通过流式细胞术对基质血管成分（SVF）细胞进行表征。
IFP体积（平均（标准差）23.6（5.4）mm）与身高相关，但与BMI或其他肥胖相关特征无关。同样，IFP脂肪细胞的体积和大小（平均271 pl，平均1933μm）与BMI无关。在IFP中观察到的CLS很少，超重/肥胖个体和瘦个体之间没有差异。此外，高BMI与IFP中较高的SVF免疫细胞数量无关，也与它们的表型变化无关。除了高BMI时TNFα表达增加外，未观察到与BMI相关的分子差异。IFP中的巨噬细胞大多具有促炎作用，产生IL-6和TNFα，但很少产生IL-10。然而，有趣的是，CD206和CD163与抗炎表型相关，是巨噬细胞上表达最丰富的表面标志物（分别为81%和41%），且CD163巨噬细胞比其CD163对应物具有更活化和促炎的表型。
在OA患者的IFP中未检测到通常在SCAT和内脏脂肪组织中观察到的与BMI相关的特征，IFP是一个与OA发病机制有关的脂肪库。
