ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 323

Anti-Inflammatory Marine Compound, Lyy-B2, Ameliorates Rheumatoid Arthritis through Inhibition of Osteoclast Differentiation

Yen-You Lin1, Hsin-Pai Lee1,2, Shi-Ying Huang1, Han-Chun Hung3, Chien-Wei Feng3, Chun-Hong Chen3, Jui-Hsin Su4,5, Ping-Jyun Sung4,5, Jyh-Horng Sheu1,3, Yen-Hsuan Jean2 and Zhi-Hong Wen1,3, 1Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-Sen University, Kaohsiung, Taiwan, 2Section of Orthopedic Surgery, Pingtung Christian Hospital, Pingtung, Taiwan, 3Doctoral Degree Program in Marine Biotechnology, National Sun Yat-Sen University, Kaohsiung, Taiwan, 4Graduate Institute of Marine Biotechnology, National Dong Hwa University, Pingtung, Taiwan, 5Taiwan Coral Research Center, National Museum of Marine Biology & Aquarium, Pingtung, Taiwan

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords:

Session Information

Title: Rheumatoid Arthritis - Animal Models

Session Type: Abstract Submissions (ACR)

Background/Purpose:

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.

Methods:

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.

Results:

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.

Conclusion:

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.

Disclosure:

Y. Y. Lin,
None;

H. P. Lee,
None;

S. Y. Huang,
None;

H. C. Hung,
None;

C. W. Feng,
None;

C. H. Chen,
None;

J. H. Su,
None;

P. J. Sung,
None;

J. H. Sheu,
None;

Y. H. Jean,
None;

Z. H. Wen,
None.

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