1 alpha ,25-Dihydroxyvitamin D sub(3) inhibits cell growth and chondrogenesis of a clonal mouse EC cell line, ATDC5

Here we report the effects of 1 alpha ,25-dihydroxyvitamin D sub(3) [1,25(OH) sub(2)D sub(3)] in vitro on the growth and chondrogenesis of a chondroprogenitor-like clonal mouse EC cell line, 10 super(-10) to 10 super(-7) M ATDC5. 1,25(OH) sub(2)D sub(3) inhibited [ super(3)H]thymidine incorporation in undifferentiated chondroprogenitor-like ATDC5 cells in time- and dose-dependent manners. 1,25(OH) sub(2)D sub(3) suppressed cartilage-nodule formation and the accumulation of cartilage-specific proteoglycan in ATDC5 cells in a dose-dependent manner. The 1,25(OH) sub(2)D sub(3)-induced inhibition of cartilage-nodule formation was reversible and direct, unrelated to the antiproliferative action of the hormone on the undifferentiated ATDC5 cells. ATDC5 cells even in the precartilaginous stage expressed 4.4 kb vitamin D receptor (VDR) mRNA as assessed by northern blot analysis. The equilibrium saturation binding experiment revealed the presence of a single class of saturable and high-affinity binding sites for 1,25(OH) sub(2)D sub(3) in the cytosols. These results provide evidence for the hypothesis that both recruitment and chondrogenesis of chondroprogenitors are negatively regulated by 1,25(OH) sub(2)D sub(3) via a VDR-mediated process in vivo.