{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T07:09:34Z","timestamp":1774422574624,"version":"3.50.1"},"reference-count":60,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T00:00:00Z","timestamp":1550620800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, we found a strict bone association between Fibroblast growth factor 23 (FGF23) and Fetuin-A, both involved in cardiovascular and mineral bone disorders. In this study, an uninvestigated bone marrow positivity for both was found. Though the role of exogenous FGF23 on mesenchymal cells (MSCs) was reported, no information is as yet available on the possible production of this hormone by MSCs. To further analyze these uninvestigated aspects, we studied human primary cells and mouse and human cell lines by means of immunostaining, qRT-PCR, enzyme linked immunosorbent assays, chromatin immunoprecipitation, transfection, and a streamlined approach for the FGF23\u2013Fetuin-A interaction called Duolink proximity ligation assay. Mesenchymal cells produce but do not secrete FGF23 and its expression increases during osteo-differentiation. Fibroblast growth factor 23 is also involved in the regulation of Fetuin-A by binding directly to the Fetuin-A promoter and then activating its transcription. Both FGF23 overexpression and addition induced an upregulation of Fetuin-A in the absence of osteo-inducer factors. Fibroblast growth factor 23 and Fetuin-A promoter were increased by osteo-inducer factors with this effect being abolished after FGF23 silencing. In conclusion, both FGF23 and Fetuin-A are present and strictly linked to each other in MSCs with FGF23 driving Fetuin-A production. This mechanism suggests a role for these two proteins in the osteoblast differentiation.<\/jats:p>","DOI":"10.3390\/ijms20040915","type":"journal-article","created":{"date-parts":[[2019,2,20]],"date-time":"2019-02-20T11:45:39Z","timestamp":1550663139000},"page":"915","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["FGF23 and Fetuin-A Interaction and Mesenchymal Osteogenic Transformation"],"prefix":"10.3390","volume":"20","author":[{"given":"Deborah","family":"Mattinzoli","sequence":"first","affiliation":[{"name":"Renal Research Laboratory Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9835-9991","authenticated-orcid":false,"given":"Masami","family":"Ikehata","sequence":"additional","affiliation":[{"name":"Renal Research Laboratory Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3341-7043","authenticated-orcid":false,"given":"Koji","family":"Tsugawa","sequence":"additional","affiliation":[{"name":"Renal Research Laboratory Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3860-5219","authenticated-orcid":false,"given":"Carlo M.","family":"Alfieri","sequence":"additional","affiliation":[{"name":"Renal Research Laboratory Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Unit of Nephrology, Dialysis and Renal transplant Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2225-897X","authenticated-orcid":false,"given":"Mario","family":"Barilani","sequence":"additional","affiliation":[{"name":"EPIGET LAB, Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"},{"name":"Department of Transfusion Medicine and Hematology, Cell Factory, Regenerative medicine laboratory, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9434-4538","authenticated-orcid":false,"given":"Lorenza","family":"Lazzari","sequence":"additional","affiliation":[{"name":"Department of Transfusion Medicine and Hematology, Cell Factory, Regenerative medicine laboratory, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola","family":"Andreetta","sequence":"additional","affiliation":[{"name":"Renal Research Laboratory Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4643-3843","authenticated-orcid":false,"given":"Francesca M.","family":"Elli","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Endocrinology Unit, University of Milan, 20122 Milan, Italy"},{"name":"Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giovanna","family":"Mantovani","sequence":"additional","affiliation":[{"name":"Department of Clinical Sciences and Community Health, Endocrinology Unit, University of Milan, 20122 Milan, Italy"},{"name":"Unit of Endocrinology and Metabolic Diseases, Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piergiorgio","family":"Messa","sequence":"additional","affiliation":[{"name":"Renal Research Laboratory Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Unit of Nephrology, Dialysis and Renal transplant Fondazione IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy"},{"name":"Department of Clinical Sciences and Community Health, University of Milan, 20122 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_2","first-page":"511","article-title":"Evaluation of mesenchymal stem cells following implantation in alveolar sockets: A canine safety study","volume":"20","author":"Drapeau","year":"2005","journal-title":"Int. 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