Articular Inflammation Is Protected By Fat-1 During The Acute Phase Of Arthritis In Mice

Sang-Il Lee¹, Yun-Hong Cheon², Ji-Min Kim³ and Won Seok Lee², ¹Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University School of Medicine, Jinju, South Korea, ²Rheumatology, Department of Internal Medicine, Chonbuk National University Medical School and Research Institute of Clinical Medicine, Jeonju, South Korea, ³Division of Rheumatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, South Korea

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: Animal models, inflammatory arthritis, osteoclasts, rheumatoid arthritis (RA) and rheumatoid arthritis

Session Information

Title: Rheumatoid Arthritis - Animal Models II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Omega-3 polyunsaturated fatty acids (n-3 PUFA) are well known to exert anti-inflammatory effects. The Fat-1 transgenic (Fat-1 TG) mice are capable of producing n-3 PUFA from the n-6 type and are emerging as a new tool for studying the role of n-3 PUFA without the interference of the potential confounding factors of diet. Therefore, this study was carried out to evaluate whether Fat-1 over-expression attenuate arthritis severity in passive K/BxN murine arthritis.

Methods: K/BxN serum transfer arthritis was induced in Fat-1 TG and age-matched wild type (WT) mice. Arthritis severity was assessed by clinical and histopathologic scoring. The levels of inflammatory cytokines in the joints and serum were measured by quantitative PCR and ELISA. The effect of Fat-1 on osteoclastogenesis was assessed using bone marrow monocytes (BMMs) and cytokine expression was assessed using fibroblast-like synoviocytes (FLS) from Fat-1 TG or WT mice.

Results: In the K/BxN serum transfer model, Fat-1 TG mice had significantly less severe arthritis than WT until day 6. The clinical scores were: 3.3 ± 0.5 in Fat-1 TG and 5.7 ± 0.3 in WT; p < 0.01) and the ankle diameter were: 2.17 ± 0.03 mm in Fat-1 TG and 2.35 ± 0.03 mm in WT; p < 0.01). The ankle joints from Fat-1 TG mice showed significantly decreased inflammation and bone erosion than WT (scores = 0.75 ± 0.2 and 2.21 ± 0.4, for Fat-1 TG and WT, respectively; p < 0.05). These effects were paralleled by decreased levels of IL-1β, IL-6, MCP-1, and MMP-3. The BMMs of Fat-1 TG mice resulted in reduced osteoclastogenesis than WT. TNF-α stimulated FLS of Fat-1 TG mice displayed lower NF-kB activity than WT, resulting in decreased transcriptional activation of proinflammatory target genes.

Conclusion: These results suggest that Fat-1 plays a critical regulatory role in the NF-kB pathway and the expression of target genes and controls articular inflammation during the acute phase of K/BxN serum transfer-induced arthritis.

Disclosure:

S. I. Lee,
None;

Y. H. Cheon,
None;

J. M. Kim,
None;

W. S. Lee,
None.

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