Suppression of arthritis-induced bone erosion by a CRAC channel antagonist

RMD Open
Harry C BlairJohn B Barnett

Abstract

We have shown in vitro and in vivo that osteoclast maturation requires calcium-release activated calcium (CRAC) channels. In inflammatory arthritis, osteoclasts mediate severe and debilitating bone erosion. In the current study, we assess the value of CRAC channels as a therapeutic target to suppress bone erosion in acute inflammatory arthritis. Collagen-induced arthritis (CIA) was induced in mice. The CRAC channel inhibitor 3,4-dichloropropionaniline (DCPA) and a placebo was administered 1 day prior to collagen II booster to induce arthritis. Effects on swelling, inflammatory cell invasion in joints, serum cytokines and bone erosion were measured. Assays, by blinded observers, of arthritis severity showed that DCPA, 21 mg/kg/day, suppressed arthritis development over 3 weeks. Bone and cartilage damage in sections of animal feet was reduced approximately 50%; overall swelling of joints was reduced by a similar amount. Effects on bone density by µCT showed clear separation in DCPA-treated CIA animals from CIA without treatment, while differences between controls without CIA and CIA treated with DCPA differed by small amounts and in most cases were not statistically different. Response was not related to anticollagen titres. Ther...Continue Reading

Citations

Jun 16, 2017·Physiology·Mohamed Trebak, James W Putney
Dec 17, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Eva M GrössingerIannis E Adamopoulos
Jun 16, 2019·Cell Calcium·Lisa J RobinsonJonathan Soboloff
Sep 20, 2018·Chemical Research in Toxicology·Rosana SchaferJohn B Barnett

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