Session Title: Rheumatoid Arthritis - Animal Models
Session Type: Abstract Submissions (ACR)
Osteoclasts are multinucleated giant cells of macrophage/monocyte lineage, and are believed to play major roles in joint destruction caused by rheumatoid arthritis (RA). Nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) is a key transcription factor which up regulates the osteoclastic-related protein expression of cathepsin K, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and tartrate-resistant acid phosphatase (TRAP), and promotes osteoclast differentiation resulting in bone resorption. In recent years, a significant number of natural products with anti-inflammatory activity have been discovered from marine organisms, and several of these compounds are now under clinical trials. In the present study, we evaluated a culture of LYY-B2, a soft coral-derived compound with anti-inflammatory and anti-arthritic properties.
We used lipopolysaccharide (LPS)-stimulated murine macrophages to evaluate the anti-inflammation and anti-osteoclast formation properties of LYY-B2, in vitro. Lewis rats (180–220g) were used to evaluate the possible effects of LYY-B2, in vivo, on adjuvant-induced arthritis (AIA) and collagen-induced arthritis (CIA) animal models. We also examine the joint features of LYY-B2 attenuation of RA by histology and immunohistochemistry.
LYY-B2 significantly inhibited pro-inflammatory induced nitric oxide synthase protein expression in LPS-stimulated macrophages. Moreover, it also attenuated multinucleated cell formation, osteoclast-related gene expression (MMP9 and cathepsin K) and expression of osteoclast-related proteins (TRAP and actin ring). Our animal experiments revealed that LYY-B2 (5mg/kg) significantly inhibited AIA and CIA joint characteristics in rats. Moreover, using histological analysis, we have found that LYY-B2 also improved the histopathologic features of RA. Immunohistochemical results show that LYY-B2 inhibited expression of osteoclast-related proteins cathepsin K, MMP 2, MMP 9, CD11b, and NFATc1 in ankle tissues of AIA- and CIA-rats.
The present findings indicated that LYY-B2 could be of potential use as a therapeutic agent to treat rheumatoid arthritis through inhibition of osteoclast differentiation.
Y. Y. Lin,
H. P. Lee,
S. Y. Huang,
H. C. Hung,
C. W. Feng,
C. H. Chen,
J. H. Su,
P. J. Sung,
J. H. Sheu,
Y. H. Jean,
Z. H. Wen,
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/anti-inflammatory-marine-compound-lyy-b2-ameliorates-rheumatoid-arthritis-through-inhibition-of-osteoclast-differentiation/