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

Abstract

We have previously reported that increased extracellular and intracellular Ca 2+ lead to adipocyte accumulation in bone marrow stromal cells (BMSCs). However, strategies to suppress high Ca 2+-enhanced adipocyte accumulation have not been reported. We examined the effects of the diacylglycerol analog phorbol 12-myristate 13-acetate (PMA) on proliferation and adipogenesis of mouse primary BMSCs. We used 9 mM CaCl 2 and 100 nM ionomycin to increase extracellular Ca 2+ and intracellular Ca 2+ , respectively. PMA suppressed the expression of both C/EBPα and PPARγ under normal adipogenesis, adipogenesis + CaCl 2 , and adipogenesis + ionomycin conditions. PMA enhanced proliferation under normal adipogenesis conditions but suppressed proliferation under adipogenesis + CaCl 2 and adipogenesis + ionomycin conditions. PMA did not affect the accumulation of adipocytes under normal adipogenesis conditions but suppressed adipocyte accumulation under adipogenesis + CaCl 2 and adipogenesis + ionomycin conditions. These results suggest that the PMA-dependent pathway is an important signaling pathway to suppress high Ca 2+-enhanced adipocyte accumulation.

Lanthanum nitrate inhibits adipogenesis in 3T3‐L1 preadipocytes with a disorder of mitotic clonal expansion process

“…On the other hand, there are still some studies with different results. Hashimoto et al (2019) found that phorbol 12‐myristate 13‐acetate suppressed adipocyte differentiation but enhance the proliferation of bone marrow stromal cells (BMSCs). A study about DNA (cytosine‐5)‐methyltransferase 3A also indicated that methylation of PPARγ promoter could decrease lipid accumulation, and methylation of p21 promoter promoted cell proliferation in porcine intramuscular preadipocytes (Qimuge et al, 2019).…”

Cross talk between 26S proteasome and mitochondria in human mesenchymal stem cells’ ability to survive under hypoxia stress

“…Mesenchymal stem cells (MSCs) are considered to be the ideal candidate in regenerative medicine [31,38]. They hold unique characteristics that place them at the top of cell therapy pyramid, including their ability to differentiate into various cell lineages; they release many cellular regulatory cytokines [6,17,39,52], and they are able to migrate to the site of injury and use their self-renewal capacity [39]. These especially distinct traits intrigue great interest in MSCs for clinical purposes which have been translated currently by having huge number of clinical studies [25,27,37,41,45].…”