title: Analysis of vitamin D metabolism gene expression in human bone: evidence for autocrine control of bone remodelling.
abstract: The metabolism of 25-hydroxyvitamin D (25D) to active 1α,25-dihydroxyvitamin D (1,25D) by endogenous expression of 25D 1-α hydroxylase (CYP27B1) in bone cells appears to have functional effects in both osteoclasts and osteoblasts. To examine relationships between CYP27B1 expression in bone and its potential function in vivo, we examined the expression of vitamin D metabolism genes (CYP27B1, CYP24A1, VDR) in human trabecular bone samples and compared them by linear regression analysis with the expression of osteoclast (TRAP, CA2, CATK, NFATC1), osteoblast (TNAP, COL1A1, OCN, MEPE, BRIL), osteocyte (DMP1, SOST, PHEX, MEPE, FGF23)-related gene markers, genes associated with osteoblast/osteocyte control of osteoclastogenesis (RANKL, M-CSF, OPG, IL-8, TWEAK) and transcription factors (NFATC1, RUNX2, OSX, MSX2, HIF1A). This revealed multiple significant gene expression relationships between CYP27B1 and the transcription factors RUNX2, NFATC1, consistent with the coordinated expression of this gene by both osteoblast and osteoclast-lineage cells, and with MSX2 and the hypoxia-inducible transcription factor, HIF1A. CYP27B1 expression associated mainly with gene markers of bone resorption. VDR mRNA expression was also associated with resorption-related genes. Against expectations, CYP27B1 expression did not associate with bone expressed genes known to be 1,25D responsive, such as OCN, RANKL and DMP1. The major implication of these relationships in gene expression is that endogenous 1,25D synthesis and the response to 1,25D in human trabecular bone is linked with coordinated functions in both the osteoclastic and osteoblastic compartments towards the control of bone remodelling. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
authors.affiliation: Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, The University of Adelaide, SA 5005, Australia.
authors.forename: Renee T
authors.initials: RT
authors.lastname: Ormsby
authors.affiliation: Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, The University of Adelaide, SA 5005, Australia.
authors.forename: David M
authors.initials: DM
authors.lastname: Findlay
authors.affiliation: Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, The University of Adelaide, SA 5005, Australia.
authors.forename: Masakazu
authors.initials: M
authors.lastname: Kogawa
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Paul H
authors.initials: PH
authors.lastname: Anderson
authors.affiliation: School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia.
authors.forename: Howard A
authors.initials: HA
authors.lastname: Morris
authors.affiliation: Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, The University of Adelaide, SA 5005, Australia. Electronic address: gerald.atkins@adelaide.edu.au.
authors.forename: Gerald J
authors.initials: GJ
authors.lastname: Atkins
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D019898:Autocrine Communication; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005786:Gene Expression Regulation; D006801:Humans; D018167:Receptors, Calcitriol / Q000235:genetics* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000235:genetics* / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
chemical_list: C000717427:FGF23 protein, human; D018167:Receptors, Calcitriol; D014807:Vitamin D; D000089703:Fibroblast Growth Factor-23; D013250:Steroid Hydroxylases; C585549:CYP24A1 protein, human; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase
keywords: Autocrine; Bone; Bone remodelling; CYP27B1; Osteocyte; Osterix; Runx2; Vitamin D