Vitamin D: Molecular mechanism of action

Sylvia Christakos, Puneet Dhawan, Bryan Benn, Angela Porta, Matthias Hediger, Goo T. Oh, Eui Bae Jeung, Yan Zhong, Dare Ajibade, Kopal Dhawan, Sneha Joshi

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

112 Scopus citations


Vitamin D maintains calcium homeostasis and is required for bone development and maintenance. Recent evidence has indicated an interrelationship between vitamin D and health beyond bone, including effects on cell proliferation and on the immune system. New developments in our lab related to the function and regulation of target proteins have provided novel insights into the mechanisms of vitamin D action. Studies in our lab have shown that the calcium-binding protein, calbindin, which has been reported to be a facilitator of calcium diffusion, also has an important role in protecting against apoptotic cell death in different tissues including protection against cytokine destruction of osteoblastic and pancreatic β cells. These findings have important implications for the therapeutic intervention of many disorders including diabetes and osteoporosis. Recent studies in our laboratory of intestinal calcium absorption using calbindin-D9k null mutant mice as well as mice lacking the 1,25-dihydroxyvitamin D3 (1,25(OH) 2D3) inducible epithelial calcium channel, TRPV6, provide evidence for the first time of calbindin-D9k and TRPV6 independent regulation of active calcium absorption. Besides calbindin, the other major target of 1,25(OH)2D3 in intestine and kidney is 25(OH)D3 24 hydroxylase (24(OH)ase), which is involved in the catabolism of 1,25(OH)2D3. In our laboratory we have identified various factors that cooperate with the vitamin D receptor in regulating 24(OH)ase expression including C/EBP β, SWI/SNF (complexes that remodel chromatin using the energy of ATP hydrolysis) and the methyltransferases, CARM1 and G9a. Evidence is also presented for C/EBP β as a nuclear coupling factor that coordinates regulation of osteopontin by 1,25(OH)2D3 and PTH. Our findings define novel mechanisms that may be of fundamental importance in understanding how 1,25(OH) 2D3 mediates its multiple biological effects.

Original languageEnglish
Title of host publicationSkeletal Biology and Medicine, Part A
Subtitle of host publicationAspects of Bone Morphogenesis and Remodeling
PublisherBlackwell Publishing Inc.
Number of pages9
ISBN (Print)9781573316842
StatePublished - Nov 2007

Publication series

NameAnnals of the New York Academy of Sciences
ISSN (Print)0077-8923
ISSN (Electronic)1749-6632


  • 1,25-dihydroxyvitamin D
  • 25-hydroxyvitamin D 24-hydroxylase
  • Calbindin
  • Osteopontin
  • Parathyroid hormone
  • TRPV6 epithelial calcium channel
  • Vitamin D


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