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The discovery that osteocytes secrete phosphaturic fibroblast growth factor 23 (FGF23) has defined bone as an endocrine organ. However, the autocrine and paracrine functions of FGF23 are still unknown. The present study focuses on the cellular and molecular mechanisms involved in the complex control of FGF23 production and local bone remodeling functions. FGF23 was assayed using ELISA kit in the presence or absence of 17β-estradiol in starved MLO-Y4 osteocytes. In these cells, a relationship between oxidative stress-induced apoptosis and up-regulation of active FGF23 levels due to MAP Kinases activation with involvement of the transcriptional factor (NF-kB) has been demonstrated. The active FGF23 increase can be due to up-regulation of its expression and post-transcriptional modifications. 17β-estradiol prevents the increase of FGF23 by inhibiting JNK and NF-kB activation, osteocyte apoptosis and by the down-regulation of osteoclastogenic factors, such as sclerostin. No alteration in the levels of dentin matrix protein 1, a FGF23 negative regulator, has been determined. The results of this study identify biological targets on which drugs and estrogen may act to control active FGF23 levels in oxidative stress-related bone and non-bone inflammatory diseases.

Titel:	Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol.
Autor/in / Beteiligte Person:	Domazetovic, V ; Falsetti, I ; Ciuffi, S ; Iantomasi, T ; Marcucci, G ; Vincenzini, MT ; Brandi, ML
Link:	Full Text Finder (Volltext)
Zeitschrift:	International journal of molecular sciences, Jg. 23 (2022-02-14), Heft 4
Veröffentlichung:	Basel, Switzerland : MDPI, [2000-, 2022
Medientyp:	academicJournal
ISSN:	1422-0067 (electronic)
DOI:	10.3390/ijms23042103
Schlagwort:	Adaptor Proteins, Signal Transducing metabolism Animals Bone Remodeling drug effects Bone and Bones drug effects Bone and Bones metabolism Cell Line Down-Regulation drug effects Estrogens metabolism Gene Expression Regulation drug effects Mice Osteocytes drug effects Osteocytes metabolism Osteogenesis drug effects Signal Transduction drug effects Up-Regulation drug effects Apoptosis drug effects Estradiol pharmacology Fibroblast Growth Factor-23 metabolism Oxidative Stress drug effects Protective Agents pharmacology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article Language: English [Int J Mol Sci] 2022 Feb 14; Vol. 23 (4). <i>Date of Electronic Publication: </i>2022 Feb 14. MeSH Terms: Apoptosis / drug effects ; Estradiol / pharmacology ; Fibroblast Growth Factor-23 / metabolism ; Oxidative Stress / drug effects ; Protective Agents / *pharmacology ; Adaptor Proteins, Signal Transducing / metabolism ; Animals ; Bone Remodeling / drug effects ; Bone and Bones / drug effects ; Bone and Bones / metabolism ; Cell Line ; Down-Regulation / drug effects ; Estrogens / metabolism ; Gene Expression Regulation / drug effects ; Mice ; Osteocytes / drug effects ; Osteocytes / metabolism ; Osteogenesis / drug effects ; Signal Transduction / drug effects ; Up-Regulation / drug effects References: Curr Osteoporos Rep. 2019 Jun;17(3):97-104. (PMID: 30915637) ; J Huazhong Univ Sci Technolog Med Sci. 2006;26(1):53-8. (PMID: 16711008) ; Pediatr Nephrol. 2013 Apr;28(4):563-8. 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(PMID: 32266417) Contributed Indexing: Keywords: FGF23; estrogen; oxidative stress-induced apoptosis Substance Nomenclature: 0 (Adaptor Proteins, Signal Transducing) ; 0 (Estrogens) ; 0 (Fgf23 protein, mouse) ; 0 (Protective Agents) ; 4TI98Z838E (Estradiol) ; 7Q7P4S7RRE (Fibroblast Growth Factor-23) Entry Date(s): Date Created: 20220226 Date Completed: 20220314 Latest Revision: 20220314 Update Code: 20231215 PubMed Central ID: PMC8879671

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Effect of Oxidative Stress-Induced Apoptosis on Active FGF23 Levels in MLO-Y4 Cells: The Protective Role of 17-β-Estradiol.