{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T00:56:14Z","timestamp":1793321774994,"version":"4.5.0"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T00:00:00Z","timestamp":1558051200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"},{"start":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T00:00:00Z","timestamp":1566777600000},"content-version":"vor","delay-in-days":101,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["asbmr.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Renal transplantation (RTx) is an effective therapy to improve clinical outcomes in pediatric patients with terminal chronic kidney disease. However, chronic immunosuppression with glucocorticoids (GCs) reduces bone growth and BMD. The mechanisms causing GC-induced growth impairment have not been fully clarified. Fibroblast growth factor 23 (FGF23) is a peptide hormone that regulates phosphate homeostasis and bone growth. In pathological conditions, FGF23 excess or abnormal FGF receptors (FGFR) activity leads to bone growth impairment. Experimental data indicate that FGF23 expression is induced by chronic GC exposure. Therefore, we hypothesize that GCs impair bone growth by increasing FGF23 expression, which has direct effects on bone growth plate. In a post hoc analysis of a multicentric randomized clinical trial of prepubertal RTx children treated with early GC withdrawal or chronic GC treatment, we observed that GC withdrawal was associated with improvement in longitudinal growth and BMD, and lower plasma FGF23 levels as compared with a chronic GC group. In prepubertal rats, GC-induced bone growth retardation correlated with increased plasma FGF23 and bone FGF23 expression. Additionally, GC treatment decreased FGFR1 expression whereas it increased FGFR3 expression in mouse tibia explants. The GC-induced bone growth impairment in tibiae explants was prevented by blockade of FGF23 receptors using either a pan-FGFR antagonist (PD173074), a C-terminal FGF23 peptide (FGF23180-205) which blocks the binding of FGF23 to the FGFR-Klotho complex or a specific FGFR3 antagonist (P3). Finally, local administration of PD173074 into the tibia growth plate ameliorated cartilage growth impairment in GC-treated rats. These results show that GC treatment partially reduces longitudinal bone growth via upregulation of FGF23 and FGFR3 expression, thus suggesting that the FGF23\/Klotho\/FGFR3 axis at the growth plate could be a potential therapeutic target for the management of GC-induced growth impairment in children.<\/jats:p>","DOI":"10.1002\/jbmr.3761","type":"journal-article","created":{"date-parts":[[2019,5,17]],"date-time":"2019-05-17T15:02:55Z","timestamp":1558105375000},"page":"1851-1861","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Glucocorticoids Decrease Longitudinal Bone Growth in Pediatric Kidney Transplant Recipients by Stimulating the FGF23\/FGFR3 Signaling Pathway"],"prefix":"10.1093","volume":"34","author":[{"given":"\u00c1ngela","family":"Delucchi","sequence":"first","affiliation":[{"name":"Division of Nephrology Cl\u00ednica Alemana de Santiago Santiago Chile"},{"name":"Division of Nephrology Hospital Luis Calvo Mackenna Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0102-9716","authenticated-orcid":false,"given":"Luis","family":"Toro","sequence":"additional","affiliation":[{"name":"Clinica Las Condes Santiago Chile"},{"name":"Centro de Investigaci\u00f3n Cl\u00ednica Avanzada Hospital Cl\u00ednico Universidad de Chile Santiago Chile"},{"name":"Division of Nephrology, Department of Medicine Hospital Cl\u00ednico Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Alzamora","sequence":"additional","affiliation":[{"name":"Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD) Santiago Chile"},{"name":"Instituto de Ciencias Biom\u00e9dicas Facultad de Medicina, Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Barrientos","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas Facultad de Medicina, Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Gonz\u00e1lez","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas Facultad de Medicina, Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo","family":"Andaur","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas Facultad de Medicina, Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Le\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas Facultad de Medicina, Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Villanueva","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas Facultad de Medicina, Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mario","family":"Galindo","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy (MIII) Santiago Chile"},{"name":"Instituto de Ciencias Biom\u00e9dicas Facultad de Medicina, Universidad de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Facundo","family":"Las Heras","sequence":"additional","affiliation":[{"name":"Department of Anatomic Pathology Hospital Cl\u00ednico Universidad de Chile Santiago Chile"},{"name":"Clinica Las Condes Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00edn","family":"Montecino","sequence":"additional","affiliation":[{"name":"FONDAP Center for Genome Regulation Universidad Andres Bello Santiago Chile"},{"name":"Institute of Biomedical Sciences, Faculty of Medicine and Faculty of Life Sciences Universidad Andr\u00e9s Bello Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Moena","sequence":"additional","affiliation":[{"name":"FONDAP Center for Genome Regulation Universidad Andres Bello Santiago Chile"},{"name":"Institute of Biomedical Sciences, Faculty of Medicine and Faculty of Life Sciences Universidad Andr\u00e9s Bello Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Lazcano","sequence":"additional","affiliation":[{"name":"Division of Nephrology Hospital de Ni\u00f1os Roberto del R\u00edo Santiago Chile"},{"name":"Division of Nephrology Cl\u00ednica Alemana de Santiago Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viola","family":"Pinto","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit Hospital Doctor Exequiel Gonz\u00e1lez Cort\u00e9s Santiago Chile"},{"name":"Clinica Las Condes Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulina","family":"Salas","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology Unit Hospital Doctor Exequiel Gonz\u00e1lez Cort\u00e9s Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Loreto","family":"Reyes","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit Pontificia Universidad Cat\u00f3lica de Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Mericq","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research, Universidad de Chile Santiago Chile"},{"name":"Clinica Las Condes Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Michea","sequence":"additional","affiliation":[{"name":"Millennium Institute on Immunology and Immunotherapy (MIII) Santiago Chile"},{"name":"Instituto de Ciencias 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