Chlormadinone acetate promotes osteoblast differentiation of human mesenchymal stem cells through the ERK signaling pathway.
Bone is continuously remodeled throughout life, and this remodeling is regulated by osteoclasts and osteoblasts. Bone-forming osteoblasts are derived from mesenchymal stem cells in bone marrow. Here, we have identified a new function of chlormadinone acetate (CMA) as an osteogenic activator in human bone marrow-derived mesenchymal stem cells (hBMSCs). To date, CMA has been used as an oral contraceptive and is known to have antiandrogenic activity. Our results show that CMA promotes osteoblast differentiation and calcium deposition in hBMSCs, whereas CMA treatment suppresses adipogenesis of hBMSCs. CMA activates and potentiates the phosphorylation of extracellular signal-regulated kinases (ERK1/2) in an osteogenic differentiation conditions. In addition, CMA-stimulated osteoblast differentiation is suppressed by inhibiting the ERK pathway, suggesting that CMA promotes the osteogenic differentiation program of hBMSCs through the ERK activation. Taken together, these results suggest a novel function of CMA as an osteogenic activator and intracellular signaling pathway mediated by CMA in osteoblast differentiation.
Jung-Min
JM
Kim
Jeung-Eun
JE
Lee
Sung Ho
SH
Ryu
Pann-Ghill
PG
Suh
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D001854:Bone Marrow Cells / Q000166:cytology; D002113:Calcification, Physiologic / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002715:Chlormadinone Acetate / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects
D015415:Biomarkers; D002715:Chlormadinone Acetate; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3