Lack of high BMI-related features in adipocytes and inflammatory cells in the infrapatellar fat pad (IFP)

Anja J. de Jong, Inge R. Klein-Wieringa, Stefan N. Andersen, Joanneke C. Kwekkeboom, Linda Herb-van Toorn, Badelog J. E. de Lange-Brokaar, Danny van Delft, John Garcia, Wu Wei, Huub J. L. van der Heide, Yvonne M. Bastiaansen-Jenniskens, Gerjo J. V. M. van Osch, Annemarie M. Zuurmond, Vedrana Stojanovic-Susulic, Rob G. H. H. Nelissen, René E. M. Toes, Margreet Kloppenburg, Andreea Ioan-Facsinay

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(3)) 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.