PMID- 26949105 OWN - NLM STAT- MEDLINE DCOM- 20170614 LR - 20191210 IS - 1879-1220 (Electronic) IS - 0960-0760 (Linking) VI - 164 DP - 2016 Nov TI - Comparison of the biological effects of exogenous and endogenous 1,25-dihydroxyvitamin D(3) on the mature osteoblast cell line MLO-A5. PG - 374-378 LID - S0960-0760(16)30050-4 [pii] LID - 10.1016/j.jsbmb.2016.03.004 [doi] AB - Clinical and animal data indicate that serum 25-hydroxyvitamin D(3) (25D) exerts an anabolic effect on bone while serum 1alpha,25-dihydroxyvitamin D(3) (1,25D) stimulates bone mineral loss, although the mechanism responsible for these divergent actions is unknown. Biological effects of 25D on bone cells are dependent on the local conversion to 1,25D by the 25-hydroxyvitamin D-1alpha-hydroxylase enzyme, CYP27B1. Therefore, identification of possible differential activities of locally produced and exogenously supplied 1,25D in bone is likely to be informative for guiding optimal administration of vitamin D supplements for bone health. The mature osteoblastic cell line MLO-A5 expresses both the vitamin D receptor (Vdr) and Cyp27b1, and therefore is a suitable model for comparing the activities of 1,25D arising from these sources. Biologically, exogenous and endogenous sources of 1,25D have similar effects on proliferation, mineralisation and induction of a range of genes by MLO-A5 osteoblasts under osteogenic conditions although endogenous 1,25D levels are markedly lower than exogenous levels. Significant differences of pharmacokinetics and pharmacodynamics of 1,25D are evident between these two sources particularly in terms of modulating gene expression for Cyp24a1 and other genes largely expressed by embedded osteoblasts/osteocytes suggesting that endogenously synthesised 1,25D is more efficiently utilised by the differentiating osteoblast. CI - Copyright (c) 2016 Elsevier Ltd. All rights reserved. FAU - Yang, Dongqing AU - Yang D AD - Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA 5005, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia. Electronic address: dongqing.yang@adelaide.edu.au. FAU - Anderson, Paul H AU - Anderson PH AD - Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia; Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia. FAU - Turner, Andrew G AU - Turner AG AD - Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia; Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia. FAU - Morris, Howard A AU - Morris HA AD - Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia; Endocrine Bone Research, Chemical Pathology, SA Pathology, Adelaide, SA 5000, Australia; Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia. FAU - Atkins, Gerald J AU - Atkins GJ AD - Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, Discipline of Orthopaedics and Trauma, University of Adelaide, Adelaide, SA 5005, Australia. LA - eng PT - Comparative Study PT - Journal Article DEP - 20160304 PL - England TA - J Steroid Biochem Mol Biol JT - The Journal of steroid biochemistry and molecular biology JID - 9015483 RN - 0 (Connexin 43) RN - 0 (GJA1 protein, mouse) RN - 0 (Receptors, Calcitriol) RN - 1406-16-2 (Vitamin D) RN - A288AR3C9H (25-hydroxyvitamin D) RN - EC 1.14.15.16 (Cyp24a1 protein, mouse) RN - EC 1.14.15.16 (Vitamin D3 24-Hydroxylase) RN - EC 1.14.15.18 (25-Hydroxyvitamin D3 1-alpha-Hydroxylase) RN - EC 3.4.24.- (Matrix Metalloproteinase 13) RN - EC 3.4.24.- (Mmp13 protein, mouse) RN - EC 4.2.1.1 (Carbonic Anhydrases) RN - FXC9231JVH (Calcitriol) SB - IM MH - 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/*genetics/metabolism MH - Animals MH - Biotransformation MH - Calcitriol/metabolism/*pharmacology MH - Carbonic Anhydrases/genetics/metabolism MH - Cell Differentiation MH - Cell Line MH - Connexin 43/genetics/metabolism MH - Gene Expression Regulation MH - Matrix Metalloproteinase 13/genetics/metabolism MH - Mice MH - Osteoblasts/cytology/*drug effects/metabolism MH - Osteocytes/cytology/*drug effects/metabolism MH - Receptors, Calcitriol/genetics/metabolism MH - Signal Transduction MH - Vitamin D/*analogs & derivatives/metabolism/pharmacology MH - Vitamin D3 24-Hydroxylase/genetics/metabolism OTO - NOTNLM OT - 25-hydroxyvitamin D(3) OT - Cyp27b1 OT - Endogenous/exogenous 1,25(OH)(2)-vitamin-D3 OT - MLO-A5 OT - Mineralisation OT - Osteogenic differentiation EDAT- 2016/03/08 06:00 MHDA- 2017/06/15 06:00 CRDT- 2016/03/08 06:00 PHST- 2015/06/15 00:00 [received] PHST- 2016/02/29 00:00 [revised] PHST- 2016/03/01 00:00 [accepted] PHST- 2016/03/08 06:00 [pubmed] PHST- 2017/06/15 06:00 [medline] PHST- 2016/03/08 06:00 [entrez] AID - S0960-0760(16)30050-4 [pii] AID - 10.1016/j.jsbmb.2016.03.004 [doi] PST - ppublish SO - J Steroid Biochem Mol Biol. 2016 Nov;164:374-378. doi: 10.1016/j.jsbmb.2016.03.004. Epub 2016 Mar 4.