1α,25-dihydroxyvitamin D3 inhibits cell growth and chondrogenesis of a clonal mouse EC cell line, ATDC5

Here we report the effects of 1α,25-dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] in vitro on the growth and chondrogenesis of a chondroprogenitor-like clonal mouse EC cell line, 10 -10 to 10 -7 M ATDC5. 1,25(OH) 2 D 3 inhibited [ 3 H] thymidine incorporation in undifferentiated chondroprogenitor-like ATDC5 cells in time- and dose-dependent manners. 1,25(OH) 2 D 3 suppressed cartilage-nodule formation and the accumulation of cartilage-specific proteoglycan in ATDC5 cells in a dose-dependent manner. The 1,25(OH) 2 D 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) 2 D 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) 2 D 3 via a VDR-mediated process in vivo.