Evidence map›Paper›PMID 22886720›Full record

ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2013

Fibroblast growth factor 23 inhibits extrarenal synthesis of 1,25-dihydroxyvitamin D in human monocytes.

Justine Bacchetta, Jessica L Sea, Rene F Chun, Thomas S Lisse, Katherine Wesseling-Perry, Barbara Gales, John S Adams, Isidro B Salusky, Martin Hewison

Open access · greenAbstract read
In one paragraph

Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
98citing papers in PubMed, 3 pooled it
7.5field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

98 citing papers in PubMed, 3 syntheses or guidelines pooled it, 189 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
    Trial
  5. Trial
  6. Randomized controlled trial of calcitriol in severe sepsis.American journal of respiratory and critical care medicine · 2014
    Trial
  7. Article
  8. Review
  9. Review
  10. Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025
    Review
  11. Article
  12. The role of nutritional vitamin D in chronic kidney disease-mineral and bone disorder in children and adults with chronic kidney disease, on dialysis, and after kidney transplantation-a European consensus statement.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2025
    Article
  13. Review
  14. Article
  15. Article
  16. Periparturient Mineral Metabolism: Implications to Health and Productivity.Animals : an open access journal from MDPI · 2024
    Review
  17. Article
  18. PKC regulates αKlotho gene expression in MDCK and NRK-52E cells.Pflugers Archiv : European journal of physiology · 2024
    Article
  19. Article
  20. The impact of vitamin D on cancer: A mini review.The Journal of steroid biochemistry and molecular biology · 2023
    Review

38 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Justine BacchettaUCLA Orthopaedic Hospital, Department of Orthopaedic Surgery, Orthopedic Hospital Research Center, David Geffen School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA.
Jessica L Sea
Rene F Chun
Thomas S Lisse
Katherine Wesseling-Perry
Barbara Gales
John S Adams
Isidro B Salusky
Martin Hewison
University of California, Los Angeles · USOrthopaedic Hospital · US

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Virology CoreP30AI028697 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CHEN, IRVIN S.Y. · 1991 to 2018
$39.9M
UCLA CLINICAL AND TRANSLATIONAL SCIENCE INSTITUTEUL1RR033176 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2011 to 2011
$15.5M
Vitamin D Metabolism in LeprosyP50AR063020 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MODLIN, ROBERT L · 2012 to 2016
$7.8M
Regulation of Bone Mineralization in Renal OsteodystrophyR01DK035423 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SALUSKY, ISIDRO B. · 1986 to 2012
$4.9M
ROLE OF PTH IN RENAL OSTEODYSTROPHYR01DK067563 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SALUSKY, ISIDRO B. · 2005 to 2009
$1.9M
FGF-23 Regulation in Chronic Kidney DiseaseK23DK080984 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WESSELING-PERRY, KATHERINE · 2009 to 2013
$872k
FGF23 and the regulation of vitamin D-induced immunity in CKDR21DK091672 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HEWISON, MARTIN · 2012 to 2013
$417k
NCATS NIH HHS UL1 TR000124NCRR NIH HHS UL1 RR033176NIAID NIH HHS P30 AI028697NIAMS NIH HHS P50 AR063020NIDDK NIH HHS DK0911672NIDDK NIH HHS DK 35423NIDDK NIH HHS DK 67563NIDDK NIH HHS DK 80984NIDDK NIH HHS K23 DK080984NIDDK NIH HHS R01 DK035423NIDDK NIH HHS R01 DK067563NIDDK NIH HHS R21 DK091672
6 · The paper itself

Abstract

Vitamin D is a potent stimulator of monocyte innate immunity, and this effect is mediated via intracrine conversion of 25-hydroxyvitamin D (25OHD) to 1,25-dihydroxyvitamin D (1,25(OH)(2) D). In the kidney, synthesis of 1,25(OH)(2) D is suppressed by fibroblast growth factor 23 (FGF23), via transcriptional suppression of the vitamin D-activating enzyme 1α-hydroxylase (CYP27B1). We hypothesized that FGF23 also suppresses CYP27B1 in monocytes, with concomitant effects on intracrine responses to 1,25(OH)(2) D. Healthy donor peripheral blood mononuclear cell monocytes (PBMCm) and peritoneal dialysate monocyte (PDm) effluent from kidney disease patients were assessed at baseline to confirm the presence of mRNA for FGF23 receptors (FGFRs), with Klotho and FGFR1 being more strongly expressed than FGFR2/3/4 in both cell types. Immunohistochemistry showed coexpression of Klotho and FGFR1 in PBMCm and PDm, with this effect being enhanced following treatment with FGF23 in PBMCm but not PDm. Treatment with FGF23 activated mitogen-activated protein kinase (MAPK) and protein kinase B (Akt) pathways in PBMCm, demonstrating functional FGFR signaling in these cells. FGF23 treatment of PBMCm and PDm decreased expression of mRNA for CYP27B1. In PBMCm this was associated with downregulation of 25OHD to 1,25(OH)(2) D metabolism, and concomitant suppression of intracrine induced 24-hydroxylase (CYP24A1) and antibacterial cathelicidin (LL37). FGF23 suppression of CYP27B1 was particularly pronounced in PBMCm treated with interleukin-15 to stimulate synthesis of 1,25(OH)(2) D. These data indicate that FGF23 can inhibit extra-renal expression of CYP27B1 and subsequent intracrine responses to 1,25(OH)(2) D in two different human monocyte models. Elevated expression of FGF23 may therefore play a crucial role in defining immune responses to vitamin D and this, in turn, may be a key determinant of infection in patients with chronic kidney disease (CKD).

Indexed as

25-Hydroxyvitamin D3 1-alpha-HydroxylaseCell SeparationFibroblast Growth Factor-23Fibroblast Growth FactorsGene Expression RegulationGlucuronidaseHumansKidneyKlotho ProteinsMonocytesPeritoneal DialysisReceptors, Fibroblast Growth FactorRNA, MessengerSignal TransductionVitamin D1,25-dihydroxyvitamin D25-Hydroxyvitamin D3 1-alpha-HydroxylaseFGF23 protein, humanFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseKlotho ProteinsReceptors, Fibroblast Growth FactorRNA, MessengerVitamin D

Identifiers

PMID22886720
PMCPMC3511915
OpenAlexW2023869058

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.