KCNK1 inhibits osteoclastogenesis via blocking Ca2+ oscillation/JNK-NFATc1 signaling axis

Abstract

KCNK1 (K+ channel, subfamily K, member 1) is a member of the inwardly rectifying K+ channel family driving the membrane potential towards the potassium balance potential. Here, we investigated its functional relevance to osteoclast differentiation. KCNK1 was significantly induced during osteoclast differentiation, but its functional overexpression significantly inhibited the RANKL-induced osteoclast differentiation accompanied with the attenuation of the RANKL-induced Ca2+ oscillation, JNK activation and NFATc1 expression. In contrast, KCNK1 knockdown enhanced the RANKL-induced osteoclast differentiation, JNK activation and NFATc1 expression. In conclusion, we suggested KCNK1 as a negative regulator of osteoclast differentiation; the increase of K+ influx by its functional blockade might inhibit osteoclast differentiation through inhibiting Ca2+ oscillation/JNK-NFATc1 signaling axis. Together with the increase of attention about the pharmacologic relevance of channel inhibition to the treatment of osteoclast-related disorders, further understanding for the functional roles and mechanisms of K+ channels underlying osteoclast-related diseases could be helpful to develop the relevant therapeutic strategy.