An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes

Itoh Y, Hatano N, Hayashi H, Onozaki K, Miyazawa K, Muraki K. An environmental sensor, TRPV4 is a novel regulator of intracellular Ca2+ in human synoviocytes. Am J Physiol Cell Physiol 297: C1082-C1090, 2009. First published September 16, 2009; doi:10.1152/ajpcell.00204.2009.-The activation of a vanilloid type 4 transient receptor potential channel (TRPV4) has an obligatory role in regulation of intracellular Ca2+ (Ca-i(2+)) in several types of cells including vascular and sensory organs. In this study, we provide evidence that TRPV4 is a functional regulator of Ca-i(2+) in human synoviocytes. Although significant expression of TRPV4 in synoviocytes from patients with (RA) and without (CTR) rheumatoid arthritis was detected at mRNA and protein level, those in the human fibroblast-like synoviocyte line MH7A were rather lower. Consistently, the selective TRPV4 agonist 4 alpha-phorbol 12,13-didecanoate (4 alpha PDD) effectively elevated Ca-i(2+) in the RA and CTR cells, which was abolished by the removal of external Ca2+. Moreover, the elevation was inhibited by ruthenium red, a blocker of TRPVs. In MH7A cells transfected with human TRPV4 (MH7A-V4), 4 alpha PDD elevated the Ca-i(2+) in a similar manner to those in the RA and CTR cells. Electrophysiological analysis also revealed that 4 alpha PDD activated nonselective cationic currents in RA cells. Application of 227 mosM solution to the RA and MH7A-V4 cells elevated their Ca-i(2+), but this does not occur when it was applied to MH7A cells. Treatment of RA but not MH7A cells with 4 alpha PDD for 24 h reduced their production of IL-8. These results suggest that an environmental sensor, TRPV4, is a novel regulator of intracellular Ca2+ in human synoviocytes.