1-ALPHA,25-DIHYDROXYVITAMIN D-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-3 [1,25(OH )(2)D-3] in vitro on the growth and chondrogenesis of a chondroprogeni tor-like clonal mouse EC cell line, 10(-10) to 10(-7) M ATDC5. 1,25(OH )(2)D-3 inhibited [H-3]thymidine incorporation in undifferentiated cho ndroprogenitor-like ATDC5 cells in time- and dose-dependent manners. 1 ,25(OH)(2)D-3 suppressed cartilage-nodule formation and the accumulati on of cartilage-specific proteoglycan in ATDC5 cells in a dose-depende nt manner, The 1,25(OH)(2)D-3-induced inhibition of cartilage-nodule f ormation nas reversible and direct, unrelated to the antiproliferative action of the hormone on the undifferentiated ATDC5 cells, ATDC5 cell s even in the precartilaginous stage expressed 4.4 lib vitamin D recep tor (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 r egulated by. 1,25(OH)(2)D-3 via a VDR-mediated process in vivo.