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

FASEB J. 2006 Nov;20(13):2417-9. doi: 10.1096/fj.06-6374fje. Epub 2006 Oct 5.


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.

MeSH terms

  • 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*


  • Vitamin D
  • RNA
  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Calcitriol
  • Calcium