ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1449

The Efficiency of the Regulation of Ca2+ Entry through Calcium Release-Activated Calcium Channel in the Treatment of Rheumatoid Arthritis

Shuang Liu1, Hitoshi Hasegawa2, Takeshi Kiyoi3, Tatsuya Sawasaki4 and Kazutaka Maeyama5, 1Dept. Pharmacology,, Ehime University Graduate School of Medicine, Toon-shi, Japan, 2Department of Bioregulatory Medicine, Ehime University Graduate School of Medicine, Toon, Japan, 3Bioscience, Integrated Center for Sciences, Ehime University, Ehime, Japan, 4Division of Cell-Free Sciences, Proteo-Science Center, Ehime University, Matsuyama, Japan, 5Department of Pharmacology, Informational Biomedicine, Ehime University Graduate School of Medicine, Toon-shi, Ehime, Japan

Meeting: 2016 ACR/ARHP Annual Meeting

Date of first publication: September 28, 2016

Keywords: , , ,

Session Information

Date: Monday, November 14, 2016

Session Title: Rheumatoid Arthritis – Animal Models - Poster II

Session Type: ACR Poster Session B

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

Background/Purpose:  The regulation of Ca2+ entry by targeting a store-operated calcium release-activated channel (CRAC), known as ORAI, has shown benefits in the treatment of rheumatoid arthritis (RA). This study was undertaken to investigate the feasibility and efficiency of CRAC inhibitors in the treatment of RA.

Methods:  Peripheral T cells and B cells were obtained from RA patients and health donors. We engrafted pannus tissue from synovia, articular cartilage, bone, and peripheral blood mononuclear cells from RA patients who underwent prosthetic replacement arthroplasty for therapeutic purposes into NOD/ShiJic-scid mice (SCID-HuRAg mice) and treated them with CRAC inhibitors, including YM-58483, a specific short hairpin RNA and a monoclonal neutralizing antibody.

Results:  The treatment of CRAC inhibitors suppressed the Ca2+ entry and the activation in peripheral cells. CRAC inhibitors declined the production of human IgG2 and IgM in SCID-HuRAg mice. According to the results of histological evaluation, treatment of SCID-HuRAg mice with CRAC inhibitors markedly suppressed invasion of synovial tissue into cartilage. A decrease in mature osteoclast activity was also observed in CRAC inhibitor-treated SCID-HuRAg mice.

Conclusion:  These results indicate that the regulation of Ca2+ entry through CRAC channel is beneficial in the treatment of RA.

Disclosure: S. Liu, None; H. Hasegawa, None; T. Kiyoi, None; T. Sawasaki, None; K. Maeyama, None.

To cite this abstract in AMA style:

Liu S, Hasegawa H, Kiyoi T, Sawasaki T, Maeyama K. The Efficiency of the Regulation of Ca2+ Entry through Calcium Release-Activated Calcium Channel in the Treatment of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2016; 68 (suppl 10). https://acrabstracts.org/abstract/the-efficiency-of-the-regulation-of-ca2-entry-through-calcium-release-activated-calcium-channel-in-the-treatment-of-rheumatoid-arthritis/. Accessed March 7, 2021.

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