ArticlePloS one2014
Osteocyte-specific deletion of Fgfr1 suppresses FGF23.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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.
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.
Who cites it
77 citing papers in PubMed, 111 citations in OpenAlex.
- Phosphate homeostasis and endocrine regulators.Pediatric nephrology (Berlin, Germany) · 2026Review
- Fibroblast growth factor receptor signaling in maturing osteoblasts controls cell-matrix interactions critical for osteocyte survival.Bone research · 2026Article
- FGFR1 signaling in rheumatoid arthritis: Mechanisms of bone destruction and therapeutic targeting (Review).International journal of molecular medicine · 2026Review
- Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation.Molecular metabolism · 2026Review
- Fibroblast Growth Factor Receptor Signaling in Maturing Osteoblasts Controls Cell-Matrix Interactions Critical for Osteocyte Survival.bioRxiv : the preprint server for biology · 2026Article
- GLP-2 alleviates postmenopausal osteoporosis by acting on osteoblasts through the PI3K/AKT/FOXO1 signalling pathway to downregulate FGF23 expression.Journal of orthopaedic surgery and research · 2026Article
- TGFβ signaling regulates the response of the skeleton to phosphate.bioRxiv : the preprint server for biology · 2025Article
- Disruption of the FGFR1-FGF23-Phosphate Axis and Targeted Therapy in a Murine Model of Osteoglophonic Dysplasia.bioRxiv : the preprint server for biology · 2025Article
- Osteocytes: master orchestrators of skeletal homeostasis, remodeling, and osteoporosis pathogenesis.Frontiers in cell and developmental biology · 2025Review
- Epithelial-like transport of mineral distinguishes bone formation from other connective tissues.Journal of cellular biochemistry · 2023Review
- Impaired Growth Plate Maturation in XLH Is due to Both Excess FGF23 and Decreased 1,25-Dihydroxyvitamin D Signaling.Endocrinology · 2023Article
- X-linked hypophosphatemia, fibroblast growth factor 23 signaling, and craniosynostosis.Experimental biology and medicine (Maywood, N.J.) · 2023Review
- FGF23 alleviates neuronal apoptosis and inflammation, and promotes locomotion recovery via activation of PI3K/AKT signalling in spinal cord injury.Experimental and therapeutic medicine · 2023Article
- Murine models of HRAS-mediated cutaneous skeletal hypophosphatemia syndrome suggest bone as the FGF23 excess source.The Journal of clinical investigation · 2023Article
- Regulation of FGF23 production and phosphate metabolism by bone-kidney interactions.Nature reviews. Nephrology · 2023Review
- Cellular dynamics of distinct skeletal cells and the development of osteosarcoma.Frontiers in endocrinology · 2023Review
- Paracrine and endocrine functions of osteocytes.Clinical pediatric endocrinology : case reports and clinical investigations : official journal of the Japanese Society for Pediatric Endocrinology · 2023Review
- Pharmacological intervention of the FGF-PTH axis as a potential therapeutic for craniofacial ciliopathies.Disease models & mechanisms · 2022Article
- New developments in the biology of fibroblast growth factors.WIREs mechanisms of disease · 2022Review
- The regulation of FGF23 under physiological and pathophysiological conditions.Pflugers Archiv : European journal of physiology · 2022Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Increases in fibroblastic growth factor 23 (FGF23 or Fgf23) production by osteocytes result in hypophosphatemia and rickets in the Hyp mouse homologue of X-linked hypophosphatemia (XLH). Fibroblastic growth factor (FGF) signaling has been implicated in the pathogenesis of Hyp. Here, we conditionally deleted FGF receptor 1 (FGFR1 or Fgfr1) in osteocytes of Hyp mice to investigate the role of autocrine/paracrine FGFR signaling in regulating FGF23 production by osteocytes. Crossing dentin matrix protein 1 (Dmp1)-Cre;Fgfr1null/+ mice with female Hyp;Fgfr1flox/flox mice created Hyp and Fgfr1 (Fgfr1Dmp1-cKO)-null mice (Hyp;Fgfr1Dmp1-cKO) with a 70% decrease in bone Fgfr1 transcripts. Fgfr1Dmp1-cKO-null mice exhibited a 50% reduction in FGF23 expression in bone and 3-fold reduction in serum FGF23 concentrations, as well as reductions in sclerostin (Sost), phosphate regulating endopeptidase on X chromosome (PHEX or Phex), matrix extracellular phosphoglycoprotein (Mepe), and Dmp1 transcripts, but had no demonstrable alterations in phosphate or vitamin D homeostasis or skeletal morphology. Hyp mice had hypophosphatemia, reductions in 1,25(OH)2D levels, rickets/osteomalacia and elevated FGF2 expression in bone. Compared to Hyp mice, compound Hyp;Fgfr1Dmp1-cKO-null mice had significant improvement in rickets and osteomalacia in association with a decrease in serum FGF23 (3607 to 1099 pg/ml), an increase in serum phosphate (6.0 mg/dl to 9.3 mg/dl) and 1,25(OH)2D (121±23 to 192±34 pg/ml) levels, but only a 30% reduction in bone FGF23 mRNA expression. FGF23 promoter activity in osteoblasts was stimulated by FGFR1 activation and inhibited by overexpression of a dominant negative FGFR1(TK-), PLCγ and MAPK inhibitors. FGF2 also stimulated the translation of an FGF23 cDNA transfected into osteoblasts via a FGFR1 and PI3K/Akt-dependent mechanism. Thus, activation of autocrine/paracrine FGF pathways is involved in the pathogenesis of Hyp through FGFR1-dependent regulation of FGF23 by both transcriptional and post-transcriptional mechanisms. This may serve to link local bone metabolism with systemic phosphate and vitamin D homeostasis.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.