{"doi":"10.1210/en.2013-1627","title":"Calcium Regulates FGF-23 Expression in Bone","abstract":"<jats:p>Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2−/− and Cyp27b1−/− mutant mice. Gcm2−/− mice exhibited low serum PTH and 1,25(OH)2D concentrations, hypocalcemia, and hyperphosphatemia, whereas Cyp27b1−/− mice had high PTH, undetectable 1,25(OH)2D, hypocalcemia, and hypophosphatemia. Serum FGF-23 levels were decreased in both mutant models. Doxercalciferol administration increased serum FGF-23 levels in both mutant models. PTH administration to Gcm2−/− mice also increased serum FGF-23 levels, in association with an increase in both 1,25(OH)2D and calcium concentrations. Multiple regression analysis of pooled data indicated that changes in FGF-23 were positively correlated with serum calcium and 1,25(OH)2D but not related to changes in serum phosphate concentrations. A high-calcium diet also increased serum FGF-23 concentrations in Cyp27b1−/− mice in the absence of 1,25(OH)2D and in Gcm2−/− mice with low PTH. The addition of calcium to the culture media also stimulated FGF-23 message expression in MC3T3-E1 osteoblasts. In addition, FGF-23 promoter activity in cultured osteoblasts was inhibited by the L-calcium-channel inhibitor nifedipine and stimulated by calcium ionophores. The effects of chronic low calcium to prevent 1,25(OH)2D and PTH stimulation of FGF-23 in these mutant mouse models suggest that suppression of FGF-23 plays an important physiological adaptive response to hypocalcemia.</jats:p>","journal":"Endocrinology","year":2013,"id":609031,"datarank":5.343165254042622,"base_score":4.890349128221754,"endowment":4.890349128221754,"self_citation_contribution":0.7335523692332632,"citation_network_contribution":4.609612884809359,"self_endowment_contribution":0.7335523692332632,"citer_contribution":4.609612884809359,"corpus_percentile":null,"corpus_rank":null,"citation_count":132,"citer_count":119,"citers_with_citation_signal":109,"citers_with_endowment":109,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":226415,"name":"Bing Dai","orcid":"0000-0003-4217-0369","position":1,"is_corresponding":false},{"id":404623,"name":"Aline Martin","orcid":"0000-0002-0144-9294","position":2,"is_corresponding":false},{"id":678155,"name":"Jinsong Huang","orcid":"0000-0002-1138-5802","position":3,"is_corresponding":false},{"id":335643,"name":"Xiaobin Han","orcid":null,"position":4,"is_corresponding":false},{"id":242354,"name":"L. Darryl Quarles","orcid":"0000-0002-5082-7896","position":5,"is_corresponding":false},{"id":404624,"name":"Valentin David","orcid":"0000-0001-9527-2364","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Calcium Regulates FGF-23 Expression in Bone","abstract":"<jats:p>Calcium has recently been shown to regulate fibroblast growth factor 23 (FGF-23), a bone-derived phosphate and vitamin D-regulating hormone. To better understand the regulation of FGF-23 by calcium, phosphorus, 1,25 dihydroxyvitamin D3 [1,25(OH)2D], and PTH, we examined FGF-23 expression under basal conditions and in response to PTH, doxercalciferol, or high-calcium diet treatment in Gcm2−/− and Cyp27b1−/− mutant mice. Gcm2−/− mice exhibited low serum PTH and 1,25(OH)2D concentrations, hypocalcemia, and hyperphosphatemia, whereas Cyp27b1−/− mice had high PTH, undetectable 1,25(OH)2D, hypocalcemia, and hypophosphatemia. Serum FGF-23 levels were decreased in both mutant models. Doxercalciferol administration increased serum FGF-23 levels in both mutant models. PTH administration to Gcm2−/− mice also increased serum FGF-23 levels, in association with an increase in both 1,25(OH)2D and calcium concentrations. Multiple regression analysis of pooled data indicated that changes in FGF-23 were positively correlated with serum calcium and 1,25(OH)2D but not related to changes in serum phosphate concentrations. A high-calcium diet also increased serum FGF-23 concentrations in Cyp27b1−/− mice in the absence of 1,25(OH)2D and in Gcm2−/− mice with low PTH. The addition of calcium to the culture media also stimulated FGF-23 message expression in MC3T3-E1 osteoblasts. In addition, FGF-23 promoter activity in cultured osteoblasts was inhibited by the L-calcium-channel inhibitor nifedipine and stimulated by calcium ionophores. The effects of chronic low calcium to prevent 1,25(OH)2D and PTH stimulation of FGF-23 in these mutant mouse models suggest that suppression of FGF-23 plays an important physiological adaptive response to hypocalcemia.</jats:p>","is_dataset_classified":null,"base_score":4.890349128221754,"endowment":4.890349128221754,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"24140714","pmcid":"PMC3836077","openalex_id":"https://openalex.org/W2154847129","authors":[],"funders":[{"funder_name":"NIAMS NIH HHS","grant_id":"R56 AR045955","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01-AR45955","title":null},{"funder_name":"NIAMS NIH HHS","grant_id":"R01 AR045955","title":null}],"total_grants":3,"fwci":7.0939,"citation_percentile":0.97866157,"influential_citations":0,"citation_trend":[{"year":2014,"count":12},{"year":2015,"count":16},{"year":2016,"count":14},{"year":2017,"count":10},{"year":2018,"count":11},{"year":2019,"count":16},{"year":2020,"count":6},{"year":2021,"count":9},{"year":2022,"count":10},{"year":2023,"count":12},{"year":2024,"count":8},{"year":2025,"count":2},{"year":2026,"count":5}],"oa_status":"bronze","license":null,"oa_locations":[{"url":"https://academic.oup.com/endo/article-pdf/154/12/4469/13635856/endo4469.pdf","host_type":"journal"},{"url":"https://academic.oup.com/endo/article-pdf/154/12/4469/13635856/endo4469.pdf","host_type":"publisher"},{"url":"http://academic.oup.com/endo/article-pdf/154/12/4469/13635856/endo4469.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1210/en.2013-1627","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/24140714","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/3836077","host_type":"repository"}],"fields_of_study":["Parathyroid Disorders and Treatments","Fibroblast Growth Factor Research","Vitamin D Research Studies","25-Hydroxyvitamin D3 1-alpha-Hydroxylase","Animals","Calcium","Cell Line","Dose-Response Relationship, Drug","Ergocalciferols","Fibroblast Growth Factor-23","Fibroblast Growth Factors","Gene Expression Regulation","Genotype","Mice","Mice, Knockout","Nuclear Proteins","Osteoblasts","Parathyroid Glands","Transcription Factors"],"mesh_terms":["Fibroblast Growth Factor-23","Animals","Calcium","Cell Line","Dose-Response Relationship, Drug","Ergocalciferols","Fibroblast Growth Factors","Gene Expression Regulation","Genotype","Nuclear Proteins","Osteoblasts","Parathyroid Glands","Transcription Factors","25-Hydroxyvitamin D3 1-alpha-Hydroxylase","Mice, Knockout","Mice"],"keywords":["Endocrinology","Internal medicine","Calcium","Fibroblast growth factor 23","Parathyroid hormone","Hypophosphatemia","Chemistry","Hyperphosphatemia","Basal (medicine)","Fibroblast growth factor","Biology","Medicine","Receptor"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-31T02:21:28.701875Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}