Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 121, Issue 1-2, Pages 88-97Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jsbmb.2010.03.019
Keywords
Vitamin D receptor; 1,25-Dihydroxyvitamin D-3; Calcium metabolism; Phosphate metabolism; Fibroblast growth factor 23; Klotho; CYP24A1; Osteocalcin (BGP); Osteopontin (SSP1); LRP5; TRPV6; RANKL; OPG; beta-Catenin; Hairless; S100A8; SOSTDC1
Funding
- NIDDK NIH HHS [R37 DK033351, DK33351, DK063930, R01 DK063930-36, R01 DK033351, R01 DK063930, R01 DK033351-24, R01 DK033351-24S1] Funding Source: Medline
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The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D-3 (1,25D), its high affinity renal endocrine ligand, to signal intestinal calcium and phosphate absorption plus bone remodeling, generating a mineralized skeleton free of rickets/osteomalacia with a reduced risk of osteoporotic fractures. 1,25D/VDR signaling regulates the expression of TRPV6, BGP, SPP1, LRP5, RANKL and OPG, while achieving feedback control of mineral ions to prevent age-related ectopic calcification by governing CYP24A1, PTH, FGF23, PHEX, and klotho transcription. Vitamin D also elicits numerous intracrine actions when circulating 25-hydroxyvitamin D-3, the metabolite reflecting vitamin D status, is converted to 1,25D locally by extrarenal CYP27B1, and binds VDR to promote immunoregulation, antimicrobial defense, xenobiotic detoxification, anti-inflammatory/anticancer actions and cardiovascular benefits. VDR also affects Wnt signaling through direct interaction with beta-catenin, ligand-dependently blunting beta-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating beta-catenin signaling via VDR ligand-independent mechanisms in osteoblasts and keratinocytes to function osteogenically and as a pro-hair cycling receptor, respectively. Finally, VDR also drives the mammalian hair cycle in conjunction with the hairless corepressor by repressing SOSTDC1, S100A8/S100A9, and PTHrP. Hair provides a shield against UV-induced skin damage and cancer in terrestrial mammals, illuminating another function of VDR that facilitates healthful aging. (C) 2010 Elsevier Ltd. All rights reserved.
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