title: New vitamin D less-calcemic analog affect human bone cell line and cultured vascular smooth muscle cells similar to other less-calcemic analogs.
abstract: Primary cultures of human bone and vascular cells respond to vitamin D treatment by modulation of cell proliferation measured by DNA synthesis (DNA) and energy metabolism measured by creatine kinase specific activity (CK) via binding to vitamin D receptors (VDR) which are expressed in these cells. Vitamin D compounds also modulate the response to estradiol-17β (E₂) and the expression mRNAs of estrogen receptors (ERα and ERβ), VDR, 25-hydroxy vitamin D₃ 1-α hydroxylase (1OHase) and lipoxygenases (12LO and 15LO). We now compared our newly synthesized analog: 1α,25-dihydroxy-9-methylene-19-norvitamin D₃ JK152 (JK), on bone and vascular cells compared to other analogs. Human bone cell line SaOS₂ respond to JK by increased DNA and stimulated CK dose-dependently, similar to the less-calcemic analogs CB 1093 (CB) and EB 1089 (EB). JK also up-regulated the response to E₂ in terms of DNA and CK. JK inhibited DNA synthesis and increased CK in primary human vascular smooth muscle cells (VSMC) dose-dependently similar to EB and CB. JK up regulated the response to E₂ in terms of CK with no effect on DNA. JK similar to CB and EB stimulated mRNA expression of VDR and ERα, 12LO and 15LO, with no effect on ERβ and 1OHase mRNA expression in SaOS₂ measured by real time PCR. Similar treatments of VSMC with JK, CB and EB stimulated 12LO and 15LO, VDR and ERα mRNA expression with no effect on ERβ and 1OHase mRNA expression. The results presented here demonstrate that the new vitamin D less-calcemic analog JK is similar to other analogs in its effects on human cultured cells and therefore may be used in combined hormone replacement treatment (HRT) both in vitro and in vivo.
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel. Electronic address: dalias@tasmc.health.gov.il.
authors.forename: D
authors.initials: D
authors.lastname: Somjen
authors.affiliation: Department of Chemistry, University of Warsaw, Warsaw, Poland.
authors.forename: U
authors.initials: U
authors.lastname: Kulesza
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: O
authors.initials: O
authors.lastname: Sharon
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: E
authors.initials: E
authors.lastname: Knoll
authors.affiliation: Institute of Endocrinology, Metabolism and Hypertension, Tel-Aviv Sourasky Medical Center and the Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Stern
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000096:biosynthesis; D001092:Arachidonate 12-Lipoxygenase / Q000187:drug effects; D001093:Arachidonate 15-Lipoxygenase / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002460:Cell Line; D002478:Cells, Cultured; D003402:Creatine Kinase / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000096:biosynthesis; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000096:biosynthesis
chemical_list: C587258:1,25-dihydroxy-9-methylene-19-norvitamin D3; C103436:CB 1093; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D004958:Estradiol; D004247:DNA; D001092:Arachidonate 12-Lipoxygenase; D001093:Arachidonate 15-Lipoxygenase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D003402:Creatine Kinase; D002117:Calcitriol; C078903:seocalcitol
keywords: 1OHase; ERα; ERβ; JK152; SaOS2; VDR; Vascular smooth muscle cells