Online-Ressource | |
Verfasst von: | Li, Mei [VerfasserIn] |
Hasan, Ahmed A. [VerfasserIn] | |
Chu, Chang [VerfasserIn] | |
Hocher, Johann-Georg [VerfasserIn] | |
Liu, Yvonne [VerfasserIn] | |
Zhang, Xiaoli [VerfasserIn] | |
Chen, Xin [VerfasserIn] | |
Yard, Benito A. [VerfasserIn] | |
Krämer, Bernhard [VerfasserIn] | |
Hocher, Berthold [VerfasserIn] | |
Titel: | Only bioactive forms of PTH (n-oxPTH and Met18(ox)-PTH) inhibit synthesis of sclerostin - evidence from in vitro and human studies |
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 |
E-Jahr: | 2024 |
Jahr: | 23 February 2024 |
Umfang: | 11 S. |
Illustrationen: | Illustrationen |
Fussnoten: | Gesehen am 06.08.2024 |
Titel Quelle: | Enthalten in: Pflügers Archiv |
Ort Quelle: | Berlin : Springer, 1868 |
Jahr Quelle: | 2024 |
Band/Heft Quelle: | 476(2024), 6, Seite 889-899 |
ISSN Quelle: | 1432-2013 |
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. |
DOI: | doi:10.1007/s00424-024-02928-x |
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 |
DOI: https://doi.org/10.1007/s00424-024-02928-x | |
Datenträger: | Online-Ressource |
Sprache: | eng |
Sach-SW: | Adaptor Proteins, Signal Transducing |
Animals | |
Bone Morphogenetic Proteins | |
Cell Line | |
Female | |
Genetic Markers | |
Humans | |
KTRs | |
Male | |
Methionine | |
Middle Aged | |
Non-oxidized | |
Osteoblasts | |
Oxidation-Reduction | |
Oxidized | |
Parathyroid Hormone | |
PTH | |
Rats | |
SOST | |
K10plus-PPN: | 1897929234 |
Verknüpfungen: | → Zeitschrift |