Sphingosine kinase-1 mediates androgen-induced osteoblast cell growth.
Herein we report that the lipid kinase sphingosine kinase-1 (SphK1) is instrumental in mediating androgen-induced cell proliferation in osteoblasts. Dihydrotestosterone (DHT) triggered cell growth in steroid-deprived MC3T3 cells, which was associated with a rapid stimulation of SphK1 and activation of both Akt and ERK signaling pathways. This mechanism relied on functional androgen receptor/PI3K/Akt nongenotropic signaling as pharmacological antagonists could block SphK1 stimulation by DHT and its consequences. Finally, SphK1 inhibition not only abrogated DHT-induced ERK activation but also blocked cell proliferation, while ERK inhibition had no impact, suggesting that SphK1 was critical for DHT signaling yet independently of the ERK.
Martin
Claire
C
CNRS, Institut de Pharmacologie et de Biologie Structurale, Toulouse F-31000, France.
Lafosse
Jean-Michel
JM
Malavaud
Bernard
B
Cuvillier
Olivier
O
D000728:Androgens / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation; D013196:Dihydrotestosterone / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011944:Receptors, Androgen / Q000378:metabolism; D000099157:Sphingosine Kinase
D000728:Androgens; D013196:Dihydrotestosterone; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D051057:Proto-Oncogene Proteins c-akt; D011944:Receptors, Androgen; D000099157:Sphingosine Kinase