title: 1 alpha,25-dihydroxyvitamin D3 inhibits cell growth and chondrogenesis of a clonal mouse EC cell line, ATDC5.
abstract: 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.
authors.affiliation: Department of Orthopaedic Surgery, Kyoto University Faculty of Medicine, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Akiyama
authors.forename: Y
authors.initials: Y
authors.lastname: Hiraki
authors.forename: C
authors.initials: C
authors.lastname: Shigeno
authors.forename: H
authors.initials: H
authors.lastname: Kohno
authors.forename: C
authors.initials: C
authors.lastname: Shukunami
authors.forename: T
authors.initials: T
authors.lastname: Tsuboyama
authors.forename: R
authors.initials: R
authors.lastname: Kasai
authors.forename: F
authors.initials: F
authors.lastname: Suzuki
authors.forename: J
authors.initials: J
authors.lastname: Konishi
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
mesh_terms: 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
chemical_list: D011509:Proteoglycans; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol; D013936:Thymidine