title: Regulation of CYP27B1 mRNA Expression in Primary Human Osteoblasts.
abstract: The enzyme 1α-hydroxylase (gene CYP27B1) catalyzes the synthesis of 1,25(OH)2D in both renal and bone cells. While renal 1α-hydroxylase is tightly regulated by hormones and 1,25(OH)2D itself, the regulation of 1α-hydroxylase in bone cells is poorly understood. The aim of this study was to investigate in a primary human osteoblast culture whether parathyroid hormone (PTH), fibroblast growth factor 23 (FGF23), calcitonin, calcium, phosphate, or MEPE affect mRNA levels of CYP27B1. Our results show that primary human osteoblasts in the presence of high calcium concentrations increase their CYP27B1 mRNA levels by 1.3-fold. CYP27B1 mRNA levels were not affected by PTH1-34, rhFGF23, calcitonin, phosphate, and rhMEPE. Our results suggest that the regulation of bone 1α-hydroxylase is different from renal 1α-hydroxylase. High calcium concentrations in bone may result in an increased local synthesis of 1,25(OH)2D leading to an enhanced matrix mineralization. In this way, the local synthesis of 1,25(OH)2D may contribute to the stimulatory effect of calcium on matrix mineralization.
authors.affiliation: Department of Internal Medicine/Endocrinology, VU University Medical Center, Research Institute MOVE, Amsterdam, The Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: van der Meijden
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Research Institute MOVE, PO Box 7057, 1007 MB, Amsterdam, The Netherlands.
authors.forename: H W
authors.initials: HW
authors.lastname: van Essen
authors.affiliation: Department of Trauma Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: F W
authors.initials: FW
authors.lastname: Bloemers
authors.affiliation: Department of Oral and Maxillofacial Surgery/Oral Pathology, VU University Medical Center, Academic Centre for Dentistry Amsterdam (ACTA), Amsterdam, The Netherlands.
authors.forename: E A J M
authors.initials: EA
authors.lastname: Schulten
authors.affiliation: Department of Internal Medicine/Endocrinology, VU University Medical Center, Research Institute MOVE, Amsterdam, The Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Lips
authors.affiliation: Department of Clinical Chemistry, VU University Medical Center, Research Institute MOVE, PO Box 7057, 1007 MB, Amsterdam, The Netherlands. n.bravenboer@vumc.nl.
authors.forename: N
authors.initials: N
authors.lastname: Bravenboer
mesh_terms: D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000235:genetics*; D002116:Calcitonin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D010006:Osteoblasts / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*
chemical_list: C000717427:FGF23 protein, human; D010281:Parathyroid Hormone; D012333:RNA, Messenger; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23; D002116:Calcitonin; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002118:Calcium
keywords: CYP27B1; Calcium; Fibroblast growth factor 23; Matrix extracellular phosphoglycoprotein; Parathyroid hormone; Primary human osteoblasts