Ca²⁺-Dependent Regulation of NFATc1 via KCa3.1 in Inflammatory Osteoclastogenesis.

ABSTRACT: In inflammatory arthritis, the dysregulation of osteoclast activity by proinflammatory cytokines, including TNF, interferes with bone remodeling during inflammation through Ca²⁺-dependent mechanisms causing pathological bone loss. Ca²⁺-dependent CREB/c-fos activation via Ca²⁺-calmodulin kinase IV (CaMKIV) induces transcriptional regulation of osteoclast-specific genes via NFATc1, which facilitate bone resorption. In leukocytes, Ca²⁺ regulation of NFAT-dependent gene expression oftentimes involves the activity of the Ca²⁺-activated K⁺ channel KCa3.1. In this study, we evaluate KCa3.1 as a modulator of Ca²⁺-induced NFAT-dependent osteoclast differentiation in inflammatory bone loss. Microarray analysis of receptor a

SUBMITTER: Grossinger EM 

PROVIDER: S-EPMC5815326 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature