title: Relative potencies of 1,25-(OH)(2)D(3) and 19-Nor-1,25-(OH)(2)D(2) on inducing differentiation and markers of bone formation in MG-63 cells.
abstract: 19-Nor-1,25-(OH)(2)D(2), an analog of 1,25-(OH)(2)D(3), is used to treat secondary hyperparathyroidism because it suppresses parathyroid hormone synthesis and secretion with lower calcemic and phosphatemic activities. 19-Nor-1,25-(OH)(2)D(2) is approximately 10 times less active than 1,25-(OH)(2)D(3) in promoting bone resorption, which accounts in part for the low potency of this analog in increasing serum calcium and phosphorus. Concern that 19-nor-1,25-(OH)(2)D(2) also could be less potent than 1,25-(OH)(2)D(3) on bone formation led to a comparison of the potency of both compounds on osteoblasts. In the human osteoblast-like cell line MG-63, 1,25-(OH)(2)D(3) and 19-nor-1,25-(OH)(2)D(2) had a similar potency in upregulating vitamin D receptor content and suppressing proliferation. Both sterols caused a similar reduction in DNA content and proliferating cell nuclear antigen protein expression. Time-course and dose-response studies on 1,25-(OH)(2)D(3) and 19-nor-1,25-(OH)(2)D(2) induction of the marker of bone formation, osteocalcin, showed overlapping curves. The effects on alkaline phosphatase (ALP) activity also were studied in MG-63 cells that had been co-treated with either sterol and transforming growth factor-beta, an enhancer of 1,25-(OH)(2)D(3)-induced ALP activity in this cell line. Transforming growth factor-beta alone had no effect, whereas 1,25-(OH)(2)D(3) and 19-nor-1,25-(OH)(2)D(2) increased ALP activity similarly. These studies demonstrate that 19-nor-1,25-(OH)(2)D(2) has the same potency as 1,25-(OH)(2)D(3) not only in inducing vitamin D receptor content, osteocalcin levels, and ALP activity but also in controlling osteoblastic growth. Therefore, it is unlikely that 19-nor-1,25-(OH)(2)D(2) would have deleterious effects on bone remodeling.
authors: Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors: Jane L
authors: JL
authors: Finch
authors: Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors: Adriana S
authors: AS
authors: Dusso
authors: Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors: Tricia
authors: T
authors: Pavlopoulos
authors: Renal Division, Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri.
authors: Eduardo A
authors: EA
authors: Slatopolsky
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D015415:Biomarkers; D001846:Bone Development / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004872:Ergocalciferols / Q000494:pharmacology*; D006801:Humans; D015675:Osteocalcin / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism
chemical_list: D015415:Biomarkers; D004872:Ergocalciferols; D018167:Receptors, Calcitriol; D015675:Osteocalcin; C003564:1,25-dihydroxyergocalciferol; C084656:paricalcitol; D000469:Alkaline Phosphatase