Regulation of fetal hemoglobin expression during hematopoietic stem cell development and its importance in bone metabolism and osteoporosis.

Details

Serval ID
serval:BIB_B4234C69BEE8
Type
Article: article from journal or magazin.
Collection
Publications
Title
Regulation of fetal hemoglobin expression during hematopoietic stem cell development and its importance in bone metabolism and osteoporosis.
Journal
International Immunopharmacology
Author(s)
Kos O., Alexander C., Brandenburg K., Chen Z., Heini A., Heumann D., Khatri I., Mach J.P., Rietschel E.T., Tersikh A., Ulmer A.J., Waelli T., Yu K., Zähringer U., Gorczynski R.M.
ISSN
1878-1705 (Electronic)
ISSN-L
1567-5769
Publication state
Published
Issued date
2018
Peer-reviewed
Oui
Volume
57
Pages
112-120
Language
english
Notes
Publication types: Journal Article
Publication Status: ppublish
Abstract
We have shown that an altered tissue redox environment in mice lacking either murine beta Hemoglobin major (Hgbβ <sub>ma</sub> KO) or minor (Hgbβ <sub>mi</sub> KO) regulates inflammation. The REDOX environment in marrow stem cell niches also control differentiation pathways. We investigated osteoclastogenesis (OC)/osteoblastogenesis (OB), in bone cultures derived from untreated or FSLE-treated WT, Hgbβ <sub>ma</sub> KO or Hgbβ <sub>mi</sub> KO mice. Marrow mesenchymal cells from 10d pre-cultures were incubated on an osteogenic matrix for 21d prior to analysis of inflammatory cytokine release into culture supernatants, and relative OC:OB using (TRAP:BSP, RANKL:OPG) mRNA expression ratios and TRAP or Von Kossa staining. Cells from WT and Hgbβ <sub>ma</sub> KO mice show decreased IL-1β,TNFα and IL-6 production and enhanced osteoblastogenesis with altered mRNA expression ratios and increased bone nodules (Von Kossa staining) in vitro after in vivo stimulation of mRNA expression of fetal Hgb genes (Hgbε and Hgbβ <sub>mi</sub> ) by a fetal liver extract (FSLE). Marrow from Hgbβ <sub>mi</sub> KO showed enhanced cytokine release and preferential enhanced osteoclastogenesis relative to similar cells from WT or Hgbβ <sub>ma</sub> KO mice, with no increased osteoblastogenesis after mouse treatment with FSLE. Pre-treatment of WT or Hgbβ <sub>ma</sub> KO, but not Hgbβ <sub>mi</sub> KO mice, with other molecules (rapamycin; hydroxyurea) which increase expression of fetal Hgb genes also augmented osteoblastogenesis and decreased cytokine production in cells differentiating in vitro. Infusion of rabbit anti- Hgbε or anti- Hgbβ <sub>mi</sub> , but not anti-Hgbα or anti- Hgbβ <sub>ma</sub> into WT mice from day 13 gestation for 3 weeks led to attenuated osteoblastogenesis in cultured cells. We conclude that increased fetal hemoglobin expression, or use of agents which improve fetal hemoglobin expression, increases osteoblast bone differentiation in association with decreased inflammatory cytokine release.
Keywords
Fetal hemoglobins, Inflammatory cytokines, Osteoclast/osteoblast differentiation in vitro, REDOX environment
Pubmed
Web of science
Create date
08/03/2018 18:31
Last modification date
20/08/2019 16:22
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