Evidence for auto/paracrine actions of vitamin D in bone: 1 alpha-hydroxylase expression and activity in human bone cells

M. van Driel, M. Koedam, C. J. Buurman, M. Hewison, H. Chiba, A. G. Uitterlinden, H. A. P. Pols, J. P. T. M. van Leeuwen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

182 Citations (Scopus)


Vitamin D is an important regulator of mineral homeostasis and bone metabolism. 1 alpha-Hydroxylation of 25-(OH)D-3 to form the bioactive vitamin D hormone, 1 alpha, 25-(OH)(2)D-3, is classically considered to take place in the kidney. However, 1 alpha-hydroxylase has been reported at extrarenal sites. Whether bone is a 1 alpha,25-(OH)(2)D-3 synthesizing tissue is not univocal. The aim of this study was to investigate an autocrine/paracrine function for 1 alpha,25-(OH)(2)D-3 in bone. We show that 1 alpha-hydroxlase 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 1 alpha-hydoxylase substrate 25-(OH)D-3, the osteoblasts can produce sufficient 1 alpha,25-(OH)(2)D-3 to modulate osteoblast activity, resulting in induced alkaline phosphatase ( ALP) activity, osteocalcin (OC) and CYP24 mRNA expression, and mineralization. The classical renal regulators of 1-hydroxylase, parathyroid hormone, and ambient calcium do not regulate 1 alpha-hydroxylase in osteoblasts. In contrast, interleukin (IL)-1 alpha strongly induces 1 alpha-hydroxylase. Besides the bone-forming cells, we demonstrate 1 alpha-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 1 alpha-hydoxylase unequivocally demonstrates that vitamin D can act in an auto/paracrine manner in bone.
Original languageEnglish
Pages (from-to)2417-+
Number of pages9
JournalFASEB Journal
Issue number13
Publication statusPublished - Nov 2006

Research programs

  • EMC MM-01-39-02
  • EMC NIHES-01-64-02
  • EMC OR-01-25-01


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