1 alpha,25-dihydroxyvitamin D3 inhibits cell growth and chondrogenesis of a clonal mouse EC cell line, ATDC5.
Here we report the effects of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3] 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)2D3 inhibited [3H]thymidine incorporation in undifferentiated chondroprogenitor-like ATDC5 cells in time- and dose-dependent manners. 1,25(OH)2D3 suppressed cartilage-nodule formation and the accumulation of cartilage-specific proteoglycan in ATDC5 cells in a dose-dependent manner. The 1,25(OH)2D3-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)2D3 in the cytosols. These results provide evidence for the hypothesis that both recruitment and chondrogenesis of chondroprogenitors are negatively regulated by 1,25(OH)2D3 via a VDR-mediated process in vivo.
Akiyama
H
H
Department of Orthopaedic Surgery, Kyoto University Faculty of Medicine, Japan.
Hiraki
Y
Y
Shigeno
C
C
Kohno
H
H
Shukunami
C
C
Tsuboyama
T
T
Kasai
R
R
Suzuki
F
F
Konishi
J
J
Nakamura
T
T
D000818:Animals; D002117:Calcitriol / Q000378:metabolism / Q000494:pharmacology*; D002356:Cartilage / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002999:Clone Cells; D051379:Mice; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
D011509:Proteoglycans; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol; D013936:Thymidine