title: Alterations in bone and erythropoiesis in hemolytic anemia: comparative study in bled, phenylhydrazine-treated and Plasmodium-infected mice.
abstract: Sustained erythropoiesis and concurrent bone marrow hyperplasia are proposed to be responsible for low bone mass density (BMD) in chronic hemolytic pathologies. As impaired erythropoiesis is also frequent in these conditions, we hypothesized that free heme may alter marrow and bone physiology in these disorders. Bone status and bone marrow erythropoiesis were studied in mice with hemolytic anemia (HA) induced by phenylhydrazine (PHZ) or Plasmodium infection and in bled mice. All treatments resulted in lower hemoglobin concentrations, enhanced erythropoiesis in the spleen and reticulocytosis. The anemia was severe in mice with acute hemolysis, which also had elevated levels of free heme and ROS. No major changes in cellularity and erythroid cell numbers occurred in the bone marrow of bled mice, which generated higher numbers of erythroid blast forming units (BFU-E) in response to erythropoietin. In contrast, low numbers of bone marrow erythroid precursors and BFU-E and low concentrations of bone remodelling markers were measured in mice with HA, which also had blunted osteoclastogenesis, in opposition to its enhancement in bled mice. The alterations in bone metabolism were accompanied by reduced trabecular bone volume, enhanced trabecular spacing and lower trabecular numbers in mice with HA. Taken together our data suggests that hemolysis exerts distinct effects to bleeding in the marrow and bone and may contribute to osteoporosis through a mechanism independent of the erythropoietic stress.
authors.affiliation: Department of Biological Sciences, Université du Québec à Montreal, Quebec, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Moreau
authors.forename: Diane
authors.initials: D
authors.lastname: Tshikudi Malu
authors.forename: Mathieu
authors.initials: M
authors.lastname: Dumais
authors.forename: Esther
authors.initials: E
authors.lastname: Dalko
authors.forename: Véronique
authors.initials: V
authors.lastname: Gaudreault
authors.forename: Hugo
authors.initials: H
authors.lastname: Roméro
authors.forename: Corine
authors.initials: C
authors.lastname: Martineau
authors.forename: Olha
authors.initials: O
authors.lastname: Kevorkova
authors.forename: Jaime Sanchez
authors.initials: JS
authors.lastname: Dardon
authors.forename: Erin Lynn
authors.initials: EL
authors.lastname: Dodd
authors.forename: David Scott
authors.initials: DS
authors.lastname: Bohle
authors.forename: Tatiana
authors.initials: T
authors.lastname: Scorza
mesh_terms: D000743:Anemia, Hemolytic / Q000139:chemically induced / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology*; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D001842:Bone and Bones / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D041905:Erythroid Cells / Q000166:cytology / Q000473:pathology; D004920:Erythropoiesis; D005260:Female; D008288:Malaria / Q000150:complications*; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000166:cytology / Q000473:pathology; D010659:Phenylhydrazines; D010961:Plasmodium / Q000302:isolation & purification*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D010659:Phenylhydrazines; D017382:Reactive Oxygen Species; C030299:phenylhydrazine