title: Intermittent and continuous exposure to 1,25(OH)2D3 have different effects on growth plate chondrocytes in vitro.
abstract: Intermittent 1,25(OH)2D3 administration is widely used to suppress parathyroid glands in secondary (renal) hyperparathyroidism. It is unknown whether the effects of continuous and intermittent 1,25(OH)2D3 differ on vitamin D target organs other than parathyroids. Using primary cultures of rat chondrocytes (tibia) we compared the effects of continuous versus intermittent exposure to physiologic concentrations of 1 alpha,25(OH)2D3 on proliferation (radiothymidine incorporation), cell count, protein synthesis ([3H]-leucine incorporation), alkaline phosphatase activity (as a marker of differentiation) and 1 alpha,25(OH)2D3 receptor (VDR) regulation. Cells were synchronized and then exposed for variable periods to a medium containing 10% delipidated FCS and 10(-8) M to 10(-12) M 1 alpha,25(OH)2D3 (or 1 beta,25(OH)2D3 as specificity control). Intermittent (8 hr exposure every 48 hr) as well as continuous (sham washing) administration of 1 alpha,25(OH)2D3 had a biphasic effect on proliferation, that is, stimulation at low (10(-12) M) and inhibition at high (10(-8) M) concentrations. At 10(-12) M intermittent 1 alpha,25(OH)2D3 yielded higher cell counts than continuous 1,25(OH)2D3. This was seen in the log phase, which was day 3 (continuous 141 +/- 2.3% of solvent control; intermittent 185 +/- 2.0%) and in the plateau phase of growth, which was day 6 (128 +/- 2.6 vs. 169 +/- 2.7% of solvent control). Dependence on extracellular Ca is suggested by the effects of varying nominal Ca concentrations in the medium and of Ca channel blockers. Even two hours of exposure to 1 alpha,25(OH)2D3 (10(-12) M) yielded maximal activation of AP during postincubation.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Pediatrics, University of Heidelberg, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Klaus
authors.forename: B
authors.initials: B
authors.lastname: König
authors.forename: U
authors.initials: U
authors.lastname: Hügel
authors.forename: E
authors.initials: E
authors.lastname: Ritz
authors.forename: O
authors.initials: O
authors.lastname: Mehls
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D002117:Calcitriol / Q000008:administration & dosage* / Q000494:pharmacology; D002356:Cartilage / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002452:Cell Count; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D006132:Growth Plate / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D013936:Thymidine / Q000378:metabolism
chemical_list: D000469:Alkaline Phosphatase; D002117:Calcitriol; D007930:Leucine; D013936:Thymidine