Phorbol 12-myristate 13-acetate (PMA) suppresses high Ca2+-enhanced adipogenesis in bone marrow stromal cells

We have previously reported that increased extracellular and intracellular Ca2+ lead to adipocyteaccumulation in bone marrow stromal cells (BMSCs). However, strategies to suppress high Ca2+-enhanced adipocyteaccumulation have not been reported. We examined the effects of the diacylglycerol analog phorbol 12- myristate13-acetate (PMA) on proliferation and adipogenesisof mouse primary BMSCs. We used 9 mM CaCl2 and 100 nM ionomycinto increase extracellular Ca2+ and intracellular Ca2+, respectively. PMA suppressed the expression of both C/EBPα and PPARγ under normal adipogenesis, adipogenesis+ CaCl2, and adipogenesis+ ionomycinconditions. PMA enhanced proliferation under normal adipogenesisconditions but suppressed proliferation under adipogenesis+ CaCl2 and adipogenesis+ ionomycinconditions. PMA did not affect the accumulation of adipocytesunder normal adipogenesisconditions but suppressed adipocyteaccumulation under adipogenesis+ CaCl2 and adipogenesis+ ionomycinconditions. These results suggest that the PMA-dependent pathway is an important signaling pathway to suppress high Ca2+-enhanced adipocyteaccumulation.