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PMID:17023519

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Citation

van Driel, M, Koedam, M, Buurman, CJ, Hewison, M, Chiba, H, Uitterlinden, AG, Pols, HA and van Leeuwen, JP (2006) Evidence for auto/paracrine actions of vitamin D in bone: 1alpha-hydroxylase expression and activity in human bone cells. FASEB J. 20:2417-9

Abstract

Vitamin D is an important regulator of mineral homeostasis and bone metabolism. 1Alpha-hydroxylation of 25-(OH)D3 to form the bioactive vitamin D hormone, 1alpha,25-(OH)2D3, is classically considered to take place in the kidney. However, 1alpha-hydroxylase has been reported at extrarenal sites. Whether bone is a 1alpha,25-(OH)2D3 synthesizing tissue is not univocal. The aim of this study was to investigate an autocrine/paracrine function for 1alpha,25-(OH)2D3 in bone. We show that 1alpha-hydroxylase is expressed in human osteoblasts, as well as the vitamin D binding protein receptors megalin and cubilin. Functional analyses demonstrate that after incubation with the 1alpha-hydroxylase substrate 25-(OH)D3, the osteoblasts can produce sufficient 1alpha,25-(OH)2D3 to modulate osteoblast activity, resulting in induced alkaline phosphatase (ALP) activity, osteocalcin (OC) and CYP24 mRNA expression, and mineralization. The classical renal regulators of 1alpha-hydroxylase, parathyroid hormone, and ambient calcium do not regulate 1alpha-hydroxylase in osteoblasts. In contrast, interleukin (IL)-1beta strongly induces 1alpha-hydroxylase. Besides the bone-forming cells, we demonstrate 1alpha-hydroxylase activity in the bone resorbing cells, the osteoclasts. This is strongly dependent on osteoclast inducer RANKL. This study showing expression, activity, and functionality of 1alpha-hydroxylase unequivocally demonstrates that vitamin D can act in an auto/paracrine manner in bone.

Links

PubMed Online version:10.1096/fj.06-6374fje

Keywords

25-Hydroxyvitamin D3 1-alpha-Hydroxylase/genetics; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase/metabolism; Bone and Bones/enzymology; Calcitriol/metabolism; Calcium/physiology; Cell Line; Femur Head/cytology; Femur Head/enzymology; Gene Expression Regulation, Enzymologic/drug effects; Humans; Osteoblasts/enzymology; Osteoclasts/enzymology; Polymerase Chain Reaction; RNA/genetics; RNA/isolation & purification; Vitamin D/pharmacology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:CP27B

involved_in

GO:0030282: bone mineralization

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CP27B

enables

GO:0004498: calcidiol 1-monooxygenase activity

ECO:0000314: direct assay evidence used in manual assertion

F

  • occurs_in:(CL:0000062)

Seeded From UniProt

complete

HUMAN:CP27B

involved_in

GO:0036378: calcitriol biosynthetic process from calciol

ECO:0000314: direct assay evidence used in manual assertion

P

  • occurs_in:(CL:0000062)

Seeded From UniProt

complete

HUMAN:OSTCN

involved_in

GO:0001649: osteoblast differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:OSTCN

involved_in

GO:0033280: response to vitamin D

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:PPBT

involved_in

GO:0033280: response to vitamin D

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:CP24A

involved_in

GO:0001649: osteoblast differentiation

ECO:0000270: expression pattern evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:IL1B

involved_in

GO:0060559: positive regulation of calcidiol 1-monooxygenase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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