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| Verfasst von: | Li, Mei [VerfasserIn]  |
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| | Hasan, Ahmed A. [VerfasserIn] |
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| | Chu, Chang [VerfasserIn] |
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| | Hocher, Johann-Georg [VerfasserIn] |
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| | Liu, Yvonne [VerfasserIn] |
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| | Zhang, Xiaoli [VerfasserIn] |
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| | Chen, Xin [VerfasserIn] |
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| | Yard, Benito A. [VerfasserIn] |
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| | Krämer, Bernhard [VerfasserIn] |
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| | Hocher, Berthold [VerfasserIn] |
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| Titel: | Only bioactive forms of PTH (n-oxPTH and Met18(ox)-PTH) inhibit synthesis of sclerostin - evidence from in vitro and human studies |
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| Verf.angabe: | Mei Li, Ahmed A. Hasan, Chang Chu, Johann-Georg Hocher, Yvonne Liu, Xiaoli Zhang, Xin Chen, Benito Yard, Bernhard K. Krämer, Berthold Hocher |
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| E-Jahr: | 2024 |
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| Jahr: | 23 February 2024 |
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| Umfang: | 11 S. |
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| Illustrationen: | Illustrationen |
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| Fussnoten: | Gesehen am 06.08.2024 |
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| Titel Quelle: | Enthalten in: Pflügers Archiv |
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| Ort Quelle: | Berlin : Springer, 1868 |
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| Jahr Quelle: | 2024 |
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| Band/Heft Quelle: | 476(2024), 6, Seite 889-899 |
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| ISSN Quelle: | 1432-2013 |
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| Abstract: | Sclerostin (SOST) is produced by osteocytes and is known as a negative regulator of bone homeostasis. Parathyroid hormone (PTH) regulates calcium, phosphate as well as vitamin D metabolism, and is a strong inhibitor of SOST synthesis in vitro and in vivo. PTH has two methionine amino acids (positions 8 and 18) which can be oxidized. PTH oxidized at Met18 (Met18(ox)-PTH) continues to be bioactive, whereas PTH oxidized at Met8 (Met8(ox)-PTH) or PTH oxidized at Met8 and Met18 (Met8, Met18(di-ox)-PTH) has minor bioactivity. How non-oxidized PTH (n-oxPTH) and oxidized forms of PTH act on sclerostin synthesis is unknown. The effects of n-oxPTH and oxidized forms of PTH on SOST gene expression were evaluated in UMR106 osteoblast-like cells. Moreover, we analyzed the relationship of SOST with n-oxPTH and all forms of oxPTH in 516 stable kidney transplant recipients using an assay system that can distinguish in clinical samples between n-oxPTH and the sum of all oxidized PTH forms (Met8(ox)-PTH, Met18(ox)-PTH, and Met8, Met18(di-ox)-PTH). We found that both n-oxPTH and Met18(ox)-PTH at doses of 1, 3, 20, and 30 nmol/L significantly inhibit SOST gene expression in vitro, whereas Met8(ox)-PTH and Met8, Met18(di-ox)-PTH only have a weak inhibitory effect on SOST gene expression. In the clinical cohort, multivariate linear regression showed that only n-oxPTH, but not intact PTH (iPTH) nor oxPTH, is independently associated with circulating SOST after adjusting for known confounding factors. In conclusion, only bioactive PTH forms such as n-oxPTH and Met18(ox)-PTH, inhibit SOST synthesis. |
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| DOI: | doi:10.1007/s00424-024-02928-x |
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| URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
kostenfrei: Volltext: https://doi.org/10.1007/s00424-024-02928-x |
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| | DOI: https://doi.org/10.1007/s00424-024-02928-x |
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| Datenträger: | Online-Ressource |
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| Sprache: | eng |
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| Sach-SW: | Adaptor Proteins, Signal Transducing |
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| | Animals |
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| | Bone Morphogenetic Proteins |
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| | Cell Line |
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| | Female |
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| | Genetic Markers |
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| | Humans |
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| | KTRs |
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| | Male |
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| | Methionine |
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| | Middle Aged |
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| | Non-oxidized |
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| | Osteoblasts |
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| | Oxidation-Reduction |
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| | Oxidized |
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| | Parathyroid Hormone |
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| | PTH |
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| | Rats |
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| | SOST |
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| K10plus-PPN: | 1897929234 |
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| Verknüpfungen: | → Zeitschrift |
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Only bioactive forms of PTH (n-oxPTH and Met18(ox)-PTH) inhibit synthesis of sclerostin - evidence from in vitro and human studies / Li, Mei [VerfasserIn]; 23 February 2024 (Online-Ressource)
