Free Fatty Acids Promote Inflammation in Bone of Rheumatic Patients Via Osteoblast

Klaus W. Frommer¹, Andreas Schäffler², Uwe Lange^1,3, Stefan Rehart⁴, Jürgen Steinmeyer^5,6, Markus Rickert⁷, Ulf Müller-Ladner^1,8 and Elena Neumann¹, ¹Internal Medicine and Rheumatology, Justus-Liebig-University of Giessen, Kerckhoff-Klinik, Bad Nauheim, Germany, ²Department of Internal Medicine III, Endocrinology, Diabetes, Metabolism, Justus-Liebig-University of Giessen, Bad Nauheim, Germany, ³Internal Medicine and Rheumatology, Justus-Liebig-University Giessen, Kerckhoff-Klinik, Bad Nauheim, Germany, ⁴Orthopedics and Trauma Surgery, Markus-Hospital, Frankfurt, Germany, ⁵Experimental Orthopedics, Justus-Liebig-University of Giessen, Giessen, Germany, ⁶Dept Orthopedics and Experimental Orthopedics, University Hospital of Giessen and Marburg, Giessen, Germany, ⁷Dept of Orthopedics and Orthopedic Surgery, University Hospital of Giessen and Marburg, Gießen, Germany, ⁸Internal Medicine/Rheumatology, Justus-Liebig-University of Giessen, Internal Medicine and Rheumatology, Kerckhoff-Klinik, Bad Nauheim, Germany

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: Bone and osteoblasts

Session Information

Date: Monday, November 9, 2015

Title: Cytokines, Mediators, Cell-cell Adhesion, Cell Trafficking and Angiogenesis Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose:

A pathophysiological link of free fatty acids (FFA) to inflammation is supported by the observation that chronically elevated serum FFA levels as found in obese patients are associated with numerous inflammatory cardiovascular and metabolic diseases. Also, FFA have been shown to induce signaling cascades and changes in gene expression in monocytes, adipocytes and hepatocytes in vitro. However, the influence of FFA on cells of bone metabolism is largely unknown so far. As obesity is associated with a higher risk of osteoarthritis also in non-weight bearing joints and increased amounts of visceral fat are associated with lower bone density, FFA may also play a role in bone metabolism.

Therefore, our main objective was to analyze the effect of FFA on cells of bone metabolism, specifically osteoblasts, in the context of rheumatic diseases. A further objective was to examine whether Wnt or TLR signaling is involved in FFA-mediated effects in osteoblasts.

Methods:

Primary osteoblasts were isolated from cancellous bone of rheumatoid arthritis (RA) or osteoarthritis (OA) patients undergoing knee joint surgery. The osteoblasts were stimulated with saturated and unsaturated FFA. Immunoassays were used to quantify protein secretion. mRNA expression levels were quantified by real-time PCR. Mineralization activity was measured by alizarin red S staining of mineralized matrix.

Results:

FFA induced a strong secretion of the proinflammatory cytokine IL-6 and the chemokine IL-8 in cultured osteoblasts, while showing a high variability between patients (IL-6: up to 9.1-fold ↑; IL-8: up to 221-fold ↑). On the other hand, RANKL and OPG, important regulators of osteoclastogenesis and osteoclast activity, osteoblast activity markers (ALP and collagen type I) and markers of osteoblast differentiation (SOX9, RunX2, osterix, osteocalcin) were not affected by FFA stimulation. Mineralization activity of FFA stimulated osteoblasts did not change significantly. The expression of Wnt signaling molecules (axin-2 and β-catenin) also remained unchanged. However, FFA-induced IL-8 secretion could significantly be reduced by blocking TLR4 but not by blocking TLR2. Of note, both saturated and unsaturated FFA caused a pro-inflammatory response in osteoblasts.

Conclusion:

Inflammation is centrally involved in many rheumatic diseases. Increased inflammatory activity is associated with decreased bone density. Our data therefore suggest that locally increased FFA levels may promote inflammation and thus inflammation-mediated degradation of bone via osteoblasts. These effects are at least in part mediated by TLR4, while TLR2 and Wnt signaling appear not to be involved.

Disclosure: K. W. Frommer, None; A. Schäffler, None; U. Lange, None; S. Rehart, None; J. Steinmeyer, None; M. Rickert, None; U. Müller-Ladner, None; E. Neumann, None.

To cite this abstract in AMA style:

Frommer KW, Schäffler A, Lange U, Rehart S, Steinmeyer J, Rickert M, Müller-Ladner U, Neumann E. Free Fatty Acids Promote Inflammation in Bone of Rheumatic Patients Via Osteoblast [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/free-fatty-acids-promote-inflammation-in-bone-of-rheumatic-patients-via-osteoblast/. Accessed .

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