10.3389/fimmu.2019.02757.s001
Klaus W. Frommer
Klaus W.
Frommer
Rebecca Hasseli
Rebecca
Hasseli
Andreas Schäffler
Andreas
Schäffler
Uwe Lange
Uwe
Lange
Stefan Rehart
Stefan
Rehart
Jürgen Steinmeyer
Jürgen
Steinmeyer
Markus Rickert
Markus
Rickert
Kerstin Sarter
Kerstin
Sarter
Mario M. Zaiss
Mario M.
Zaiss
Carsten Culmsee
Carsten
Culmsee
Goutham Ganjam
Goutham
Ganjam
Susanne Michels
Susanne
Michels
Ulf Müller-Ladner
Ulf
Müller-Ladner
Elena Neumann
Elena
Neumann
Image_1_Free Fatty Acids in Bone Pathophysiology of Rheumatic Diseases.TIF
Frontiers
2019
fatty acid
inflammation
osteoblasts
osteoclasts
rheumatoid arthritis
osteoarthritis
2019-12-03 04:15:33
Figure
https://frontiersin.figshare.com/articles/figure/Image_1_Free_Fatty_Acids_in_Bone_Pathophysiology_of_Rheumatic_Diseases_TIF/11307704
<p>Obesity—in which free fatty acid (FFA) levels are chronically elevated—is a known risk factor for different rheumatic diseases, and obese patients are more likely to develop osteoarthritis (OA) also in non-weight-bearing joints. These findings suggest that FFA may also play a role in inflammation-related joint damage and bone loss in rheumatoid arthritis (RA) and OA. Therefore, the objective of this study was to analyze if and how FFA influence cells of bone metabolism in rheumatic diseases. When stimulated with FFA, osteoblasts from RA and OA patients secreted higher amounts of the proinflammatory cytokine interleukin (IL)-6 and the chemokines IL-8, growth-related oncogene α, and monocyte chemotactic protein 1. Receptor activator of nuclear factor kappa B ligand (RANKL), osteoprotegerin, and osteoblast differentiation markers were not influenced by FFA. Mineralization activity of osteoblasts correlated inversely with the level of FFA-induced IL-6 secretion. Expression of the Wnt signaling molecules, axin-2 and β-catenin, was not changed by palmitic acid (PA) or linoleic acid (LA), suggesting no involvement of the Wnt signaling pathway in FFA signaling for osteoblasts. On the other hand, Toll-like receptor 4 blockade significantly reduced PA-induced IL-8 secretion by osteoblasts, while blocking Toll-like receptor 2 had no effect. In osteoclasts, IL-8 secretion was enhanced by PA and LA particularly at the earliest time point of differentiation. Differences were observed between the responses of RA and OA osteoclasts. FFA might therefore represent a new molecular factor by which adipose tissue contributes to subchondral bone damage in RA and OA. In this context, their mechanisms of action appear to be dependent on inflammation and innate immune system rather than Wnt-RANKL pathways.</p>