INTERACTIONS BETWEEN RETINOIC ACID AND 1,25(OH)(2)D IN MOUSE IMMORTALIZED OSTEOBLASTIC C1 CELLS

The interactions between 1,25-dihydroxyvitamin D-3 [1,25(OH)(2)D] and retinoic acid (RA) on alkaline phosphatase (ALP) activity and vitamin D receptors (VDR) were determined in the SV40 immortalized osteoblasti c cell line C1. Biochemical and cytochemical analysis showed that ALP activity increased with C1 cell density and that 1,25(OH)(2)D inhibite d ALP activity at high density, whereas RA increased ALP activity at l ow density. The interactions of the two hormones were also cell densit y dependent, with a predominant stimulatory effect of RA at low densit y and a predominant inhibitory effect of 1,25(OH)(2)D at high density. In contrast, the two hormones inhibited C1 cell proliferation indepen dently of cell density. Scatchard analysis and immunocytochemical stai ning showed that nuclear VDR levels increased with cell density and th at RA, 1,25(OH)(2)D, and their combination upregulated VDR levels main ly at high cell density. Although RA increased VDR levels, RA did not potentiate the effect of 1,25(OH)(2)D on ALP activity. The results ind icate that the effects and interactions of 1,25(OH)(2)D and RA on ALP activity in osteoblastic C1 cells depend on the state of phenotypic ma turation.