PHYSIOLOGICAL CONCENTRATIONS OF RETINOIC ACID SUPPRESS THE OSTEOBLASTIC DIFFERENTIATION OF FETAL-RAT CALVARIA CELLS IN-VITRO

The effects of retinoic acid (RA) on osteoblastic differentiation and activity were studied in fetal rat calvaria cells cultured for up to 2 4 days. Fetal bovine serum used for the experiments was treated with a n anion-exchange resin to remove endogenous RA. The depletion of RA in the treated serum was confirmed by high-performance liquid chromatogr aphy and tritiated RA tracing. Under the culture conditions employed, the continuous presence of RA for 14 days at 10(-9) mol/l or higher de creased both alkaline phosphatase (ALP) activity on day 12 and the num ber of bone nodules on day 14 in a dose-dependent manner, Short-term ( 24h) exposure to RA at 10(-8) mol/l, which is a physiological concentr ation, decreased and increased the levels of ALP and osteopontin mRNA on day 6, respectively, Retinoic acid at 10(-8) mol/l also increased t he level of osteocalcin mRNA on day 12. However, these effects were no t obvious at later stages (days 18 and 24). At a high concentration (1 0(-6) mol/l), RA increased the level of osteopontin mRNA on day 6 and decreased the levels of ALP and osteocalcin mRNA irrespective of cultu re period. These results suggest that, at physiological concentrations , RA suppresses the differentiation of osteoprogenitor cells and regul ates osteoblastic functions.