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Regulation of fetal hemoglobin expression during hematopoietic stem cell development and its importance in bone metabolism and osteoporosis.
Kos, O; Alexander, C; Brandenburg, K; Chen, Z; Heini, A; Heumann, D; Khatri, I; Mach, J P; Rietschel, E T; Terskikh, A; Ulmer, A J; Waelli, T; Yu, K; Zähringer, U; Gorczynski, R M.
Afiliación
  • Kos O; Institute of Medical Sciences, University of Toronto, Toronto, Canada.
  • Alexander C; Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
  • Brandenburg K; Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
  • Chen Z; Institute of Medical Sciences, University of Toronto, Toronto, Canada.
  • Heini A; Clinique La Prairie, Clarens-Montreux, Switzerland.
  • Heumann D; Clinique La Prairie, Clarens-Montreux, Switzerland.
  • Khatri I; Institute of Medical Sciences, University of Toronto, Toronto, Canada.
  • Mach JP; Department of Biochemistry, University of Lausanne, Switzerland.
  • Rietschel ET; Alsterblick 14, D-22397 Hamburg, Germany.
  • Terskikh A; Sanford Burnham Prebys Medical Discovery Institute, La Jolla, California, USA.
  • Ulmer AJ; Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
  • Waelli T; Clinique La Prairie, Clarens-Montreux, Switzerland.
  • Yu K; Institute of Medical Sciences, University of Toronto, Toronto, Canada.
  • Zähringer U; Research Center Borstel, Leibniz-Center for Medicine and Biosciences, Borstel, Germany.
  • Gorczynski RM; Institute of Medical Sciences, University of Toronto, Toronto, Canada. Electronic address: reg.gorczynski@utoronto.ca.
Int Immunopharmacol ; 57: 112-120, 2018 04.
Article en En | MEDLINE | ID: mdl-29477972
We have shown that an altered tissue redox environment in mice lacking either murine beta Hemoglobin major (HgbßmaKO) or minor (HgbßmiKO) 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, HgbßmaKO or HgbßmiKO 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 HgbßmaKO mice show decreased IL-1ß,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 Hgbßmi) by a fetal liver extract (FSLE). Marrow from HgbßmiKO showed enhanced cytokine release and preferential enhanced osteoclastogenesis relative to similar cells from WT or HgbßmaKO mice, with no increased osteoblastogenesis after mouse treatment with FSLE. Pre-treatment of WT or HgbßmaKO, but not HgbßmiKO 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- Hgbßmi, but not anti-Hgbα or anti- Hgbßma 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteoporosis / Huesos / Hemoglobina Fetal / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Países Bajos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoblastos / Osteoporosis / Huesos / Hemoglobina Fetal / Células Madre Mesenquimatosas Límite: Animals Idioma: En Revista: Int Immunopharmacol Asunto de la revista: ALERGIA E IMUNOLOGIA / FARMACOLOGIA Año: 2018 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Países Bajos