All-trans retinoic acid inhibits dexamethasone-induced ALP activity and mineralization in human osteoblastic cell line SV HFO.
We have recently established a human osteoblastic cell line (SV-HFO) in a culture system, in which the cells are mineralized by treatment with dexamethasone (Dex). Using this system, we examined the effects of all trans-retinoic acid (RA) on the mineralization of the cells. RA inhibited the mineralization, coincident with the inhibition of alkaline phosphatase (ALP). On the other hand, RA induced osteocalcin secretion and had no effect on the expression of the other osteoblastic markers such as type I collagen and osteonectin. To further clarify the mechanism of inhibition of mineralization by RA, we used the retinoic acid receptor (RAR) alpha-selective (Am80), beta-selective (CD2019) and gamma-selective (CD437) agonists instead of RA. RAR alpha- and RAR beta-selective agonists inhibited the mineralization and ALP activity of the cells, while the RAR gamma-selective agonist had no such effects. On the other hand, the RAR gamma-selective agonist induced osteocalcin secretion, but RAR alpha- and RAR beta-selective agonists had no effect on osteocalcin secretion. These results suggested that the inhibitory effect of RA on the mineralization of human osteoblasts is mediated by the activation of RAR alpha and/or RAR beta and that RAR gamma preferentially regulates the expression of osteocalcin without influence on mineralization.
Nuka
S
S
Department of Pathology, Sapporo Medical University School of Medicine, Japan.
Sawada
N
N
Iba
K
K
Chiba
H
H
Ishii
S
S
Mori
M
M
D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors*; D001565:Benzoates / Q000494:pharmacology; D015415:Biomarkers; D002113:Calcification, Physiologic / Q000187:drug effects*; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D009281:Naphthalenes / Q000494:pharmacology; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids / Q000494:pharmacology; D013723:Teratogens / Q000494:pharmacology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology; D014212:Tretinoin / Q000494:pharmacology*; D000097768:Retinoic Acid Receptor gamma
D000469:Alkaline Phosphatase; D001565:Benzoates; D015415:Biomarkers; D003907:Dexamethasone; D004791:Enzyme Inhibitors; D009281:Naphthalenes; D015675:Osteocalcin; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D012176:Retinoids; D013723:Teratogens; D013764:Tetrahydronaphthalenes; D014212:Tretinoin; D000097768:Retinoic Acid Receptor gamma; C101407:CD 2019; C099555:CD 437; C000607071:RARA protein, human; C082925:retinoic acid receptor beta; C061133:tamibarotene