PC-PLC is involved in osteoclastogenesis induced by TNF-α through upregulating IP3R1 expression

The precise mechanism of how TNF-alpha promotes osteoclast formation is not clear. Previous reports show TNF-alpha targets molecules that regulate calcium signaling. Inositol-1,4,5-trisphosphate receptors (IP3Rs) are important calcium channel responsible for evoking intracellular calcium oscillation. We found that TNF-alpha increased the expression of IP3R1 and promoted osteoclastogenesis in RANKL-induced mouse BMMs. Phosphatidylcholine-specific phospholipase C (PC-PLC) specific inhibitor D609 eliminated the upregulation of IP3R1 by TNF-alpha, and decreased the autoamplification of nuclear factor of activated T-cells 1 (NFATc1), thus resulted in less osteoclasts formation. However, D609 did not inhibit RANKL-induced osteoclastogenesis. Our data suggest TNF-alpha promotes RANKL-induced osteoclastogenesis, at least partially, through PC-PLC/IP3R1/NFATc1 pathway. (C) 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.