The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the " Fountain of Youth" to mediate healthful aging

Mark R. Haussler, Carol A. Haussler, G. Kerr Whitfield, Jui Cheng Hsieh, Paul D. Thompson, Thomas K. Barthel, Leonid Bartik, Jan B. Egan, Yifei Wu, Jana L. Kubicek, Christine L. Lowmiller, Eric W. Moffet, Ryan E. Forster, Peter Jurutka

Research output: Contribution to journalArticle

115 Citations (Scopus)

Abstract

The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D3 (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 D3, 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 β-catenin, ligand-dependently blunting β-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating β-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.

Original languageEnglish (US)
Pages (from-to)88-97
Number of pages10
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume121
Issue number1-2
DOIs
StatePublished - Jul 2010

Fingerprint

Fountains
Calcitriol Receptors
Gene encoding
Aging of materials
Gene Expression
Catenins
Calcitriol
Hair
Transcription
Ligands
Vitamin D
25-Hydroxyvitamin D3 1-alpha-Hydroxylase
Calcifediol
Parathyroid Hormone-Related Protein
Co-Repressor Proteins
Osteomalacia
Detoxification
Rickets
Osteoporotic Fractures
Mammals

Keywords

  • β-Catenin
  • 1,25-Dihydroxyvitamin D
  • Calcium metabolism
  • CYP24A1
  • Fibroblast growth factor 23
  • Hairless
  • Klotho
  • LRP5
  • OPG
  • Osteocalcin (BGP)
  • Osteopontin (SSP1)
  • Phosphate metabolism
  • RANKL
  • S100A8
  • SOSTDC1
  • TRPV6
  • Vitamin D receptor

ASJC Scopus subject areas

  • Molecular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Molecular Biology
  • Cell Biology
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry
  • Medicine(all)

Cite this

The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the " Fountain of Youth" to mediate healthful aging. / Haussler, Mark R.; Haussler, Carol A.; Whitfield, G. Kerr; Hsieh, Jui Cheng; Thompson, Paul D.; Barthel, Thomas K.; Bartik, Leonid; Egan, Jan B.; Wu, Yifei; Kubicek, Jana L.; Lowmiller, Christine L.; Moffet, Eric W.; Forster, Ryan E.; Jurutka, Peter.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 121, No. 1-2, 07.2010, p. 88-97.

Research output: Contribution to journalArticle

Haussler, MR, Haussler, CA, Whitfield, GK, Hsieh, JC, Thompson, PD, Barthel, TK, Bartik, L, Egan, JB, Wu, Y, Kubicek, JL, Lowmiller, CL, Moffet, EW, Forster, RE & Jurutka, P 2010, 'The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the " Fountain of Youth" to mediate healthful aging', Journal of Steroid Biochemistry and Molecular Biology, vol. 121, no. 1-2, pp. 88-97. https://doi.org/10.1016/j.jsbmb.2010.03.019
Haussler, Mark R. ; Haussler, Carol A. ; Whitfield, G. Kerr ; Hsieh, Jui Cheng ; Thompson, Paul D. ; Barthel, Thomas K. ; Bartik, Leonid ; Egan, Jan B. ; Wu, Yifei ; Kubicek, Jana L. ; Lowmiller, Christine L. ; Moffet, Eric W. ; Forster, Ryan E. ; Jurutka, Peter. / The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the " Fountain of Youth" to mediate healthful aging. In: Journal of Steroid Biochemistry and Molecular Biology. 2010 ; Vol. 121, No. 1-2. pp. 88-97.
@article{6a691dc1e5fa45deb0cb37e96eb2fb8c,
title = "The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the {"} Fountain of Youth{"} to mediate healthful aging",
abstract = "The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D3 (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 D3, 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 β-catenin, ligand-dependently blunting β-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating β-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.",
keywords = "β-Catenin, 1,25-Dihydroxyvitamin D, Calcium metabolism, CYP24A1, Fibroblast growth factor 23, Hairless, Klotho, LRP5, OPG, Osteocalcin (BGP), Osteopontin (SSP1), Phosphate metabolism, RANKL, S100A8, SOSTDC1, TRPV6, Vitamin D receptor",
author = "Haussler, {Mark R.} and Haussler, {Carol A.} and Whitfield, {G. Kerr} and Hsieh, {Jui Cheng} and Thompson, {Paul D.} and Barthel, {Thomas K.} and Leonid Bartik and Egan, {Jan B.} and Yifei Wu and Kubicek, {Jana L.} and Lowmiller, {Christine L.} and Moffet, {Eric W.} and Forster, {Ryan E.} and Peter Jurutka",
year = "2010",
month = "7",
doi = "10.1016/j.jsbmb.2010.03.019",
language = "English (US)",
volume = "121",
pages = "88--97",
journal = "Journal of Steroid Biochemistry and Molecular Biology",
issn = "0960-0760",
publisher = "Elsevier Limited",
number = "1-2",

}

TY - JOUR

T1 - The nuclear vitamin D receptor controls the expression of genes encoding factors which feed the " Fountain of Youth" to mediate healthful aging

AU - Haussler, Mark R.

AU - Haussler, Carol A.

AU - Whitfield, G. Kerr

AU - Hsieh, Jui Cheng

AU - Thompson, Paul D.

AU - Barthel, Thomas K.

AU - Bartik, Leonid

AU - Egan, Jan B.

AU - Wu, Yifei

AU - Kubicek, Jana L.

AU - Lowmiller, Christine L.

AU - Moffet, Eric W.

AU - Forster, Ryan E.

AU - Jurutka, Peter

PY - 2010/7

Y1 - 2010/7

N2 - The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D3 (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 D3, 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 β-catenin, ligand-dependently blunting β-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating β-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.

AB - The nuclear vitamin D receptor (VDR) binds 1,25-dihydroxyvitamin D3 (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 D3, 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 β-catenin, ligand-dependently blunting β-catenin mediated transcription in colon cancer cells to attenuate growth, while potentiating β-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.

KW - β-Catenin

KW - 1,25-Dihydroxyvitamin D

KW - Calcium metabolism

KW - CYP24A1

KW - Fibroblast growth factor 23

KW - Hairless

KW - Klotho

KW - LRP5

KW - OPG

KW - Osteocalcin (BGP)

KW - Osteopontin (SSP1)

KW - Phosphate metabolism

KW - RANKL

KW - S100A8

KW - SOSTDC1

KW - TRPV6

KW - Vitamin D receptor

UR - http://www.scopus.com/inward/record.url?scp=77954761260&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77954761260&partnerID=8YFLogxK

U2 - 10.1016/j.jsbmb.2010.03.019

DO - 10.1016/j.jsbmb.2010.03.019

M3 - Article

C2 - 20227497

AN - SCOPUS:77954761260

VL - 121

SP - 88

EP - 97

JO - Journal of Steroid Biochemistry and Molecular Biology

JF - Journal of Steroid Biochemistry and Molecular Biology

SN - 0960-0760

IS - 1-2

ER -