ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2011
Bone proteins PHEX and DMP1 regulate fibroblastic growth factor Fgf23 expression in osteocytes through a common pathway involving FGF receptor (FGFR) signaling.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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Who cites it
149 citing papers in PubMed, 250 citations in OpenAlex.
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- Fibroblast growth factor 23 at the crossroads of mineral metabolism and bone disease.Current opinion in nephrology and hypertension · 2026Review
- Fibroblast growth factor 23: Regulation, signalling and systemic links between bone, metabolism and inflammation.Molecular metabolism · 2026Review
- Expanding the Autosomal Recessive Hypophosphatemic Rickets Type I Carrier Phenotype and Adult Treatment with Burosumab.Calcified tissue international · 2026Article
- Chorein Regulates Key Osteoblast Genes in UMR-106 Cells.Cell biochemistry and biophysics · 2026Article
- Current advances of bone homeostasis imbalance in the cause of hereditary metabolic bone diseases.EFORT open reviews · 2026Review
- DMP1-Mediated FAK Activation Contributes to P Utilization of Broiler Osteoblasts by Suppressing FGF23 Expression.Biology · 2026Article
- 3D Osteocyte Networks under Pulsatile Unidirectional Fluid Flow Stimuli (PUFFS).ACS biomaterials science & engineering · 2025Article
- High fat diet induces gastric production of fibroblast growth factor 23 (FGF23).International journal of obesity (2005) · 2025Article
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- Connecting Bone Remodeling and Regeneration: Unraveling Hormones and Signaling Pathways.Biology · 2025Review
- Emerging concepts on the FGF23 regulation and activity.Molecular and cellular biochemistry · 2025Review
- Effect of Mutation Type on Ectopic Ossification Among Adult Patients With X-Linked Hypophosphatemia.Journal of the Endocrine Society · 2024Article
- Sclerostin and Wnt Signaling in Idiopathic Juvenile Osteoporosis Using High-Resolution Confocal Microscopy for Three-Dimensional Analyses.Children (Basel, Switzerland) · 2024Article
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- Sclerostin antibody improves alveolar bone quality in the Hyp mouse model of X-linked hypophosphatemia (XLH).International journal of oral science · 2023Article
- Generation of bicistronic Dmp1-Cre knock-in mice using a self-cleaving 2A peptide.Journal of bone and mineral metabolism · 2023Article
- Transcription factor HNF4α2 promotes osteogenesis and prevents bone abnormalities in mice with renal osteodystrophy.The Journal of clinical investigation · 2023Article
- Pathogenic mechanisms of glucocorticoid-induced osteoporosis.Cytokine & growth factor reviews · 2023Review
- Wnt pathway inhibitors are upregulated in XLH dental pulp cells in response to odontogenic differentiation.International journal of oral science · 2023Article
89 more citing papers are in PubMed but not listed here.
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7 authors at 3 institutions in 1 country.
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Abstract
Fibroblastic growth factor 23 (FGF23) is a circulating phosphaturic hormone. Inactivating mutations of the endopeptidase PHEX or the SIBLING protein DMP1 result in equivalent intrinsic bone mineralization defects and increased Fgf23 expression in osteocytes. The mechanisms whereby PHEX and DMP1 regulate Fgf23 expression are unknown. We examined the possibility that PHEX and DMP1 regulate Fgf23 through a common pathway by analyzing the phenotype of compound Phex and Dmp1 mutant mice (Hyp/Dmp1(-/-)). Compared to single-mutant littermates, compound-mutant Hyp/Dmp1(-/-) mice displayed nonadditive elevations of serum FGF23 (1912 ± 183, 1715 ± 178, and 1799 ± 181 pg/ml), hypophosphatemia (P(i): 6.0 ± 0.3, 5.8 ± 0.2, and 5.4 ± 0.1 mg/dl), and severity of rickets/osteomalacia (bone mineral density: -36, -36, and -30%). Microarray analysis of long bones identified gene expression profiles implicating common activation of the FGFR pathway in all the mutant groups. Furthermore, inhibiting FGFR signaling using SU5402 in Hyp- and Dmp1(-/-)-derived bone marrow stromal cells prevented the increase in Fgf23 mRNA expression (129- and 124-fold increase in Hyp and Dmp1(-/-) vs. 1.3-fold in Hyp+SU5402 and 2.5-fold in Dmp1(-/-)+SU5402, P<0.05). For all analyses, samples collected from nonmutant wild-type littermates served as controls. These findings indicate that PHEX and DMP1 control a common pathway regulating bone mineralization and FGF23 production, the latter involving activation of the FGFR signaling in osteocytes.
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