Separate and combined effects of hypobaric hypoxia and hindlimb suspension on skeletal homeostasis and hematopoiesis in mice.
hematopoietic stem and progenitor cells
hindlimb suspension
hypobaric hypoxia
mesenchymal stromal cells
Journal
Hypoxia (Auckland, N.Z.)
ISSN: 2324-1128
Titre abrégé: Hypoxia (Auckl)
Pays: New Zealand
ID NLM: 101617967
Informations de publication
Date de publication:
2019
2019
Historique:
received:
23
11
2018
accepted:
15
02
2019
entrez:
24
8
2019
pubmed:
24
8
2019
medline:
24
8
2019
Statut:
epublish
Résumé
Bone marrow response to an organismal stress is made by orchestrating the interplay between hematopoietic stem/progenitor cells (HSPCs) and mesenchymal stromal cells (MSCs). Neither the cellular nor the molecular factors that regulate this process are fully understood, especially since this mechanism probably varies depending on the type of stress. Herein, we explored the differentiation and fate of MSCs and HSPCs in mice challenged with a hematopoietic stress or a mechanical stress applied separately or in combination. Mice were subjected to 4 days of hypobaric hypoxia (hematopoietic challenge) and/or 7 days of hindlimb suspension (stromal challenge) and then sacrificed for blood and bone collection. Using hematological measurements, colony-forming unit assays, bone histomorphometry and array-based multiplex ELISA analysis, we evaluated challenge influences on both MSC and HSPC mobilization, differentiation (osteoblasts, osteoclasts, and mature blood cells) and fate. We found that hypoxia leads to HSPC mobilization and that an imbalance between bone formation and bone resorption accounts for this mobilization. Whilst suspension is also associated with an imbalance between bone formation and bone resorption, it does not induce HSPC mobilization. Then, we revealed cellular interactions by combining hematopoietic and stromal challenges together in mice. We showed that the hypoxia-driven HSPC mobilization is moderated by suspension. Moreover, when applied in a hypoxic environment, suspension offsets bone imbalance. We identified stroma cell-derived factors MIP-1α, HGF and SDF-1 as potent molecular key players sustaining interactions between hindlimb suspension and hypobaric hypoxia. Taken together, our data highlight the benefit of combining different types of stress to better understand the interplay between MSCs and HSPCs.
Identifiants
pubmed: 31440522
doi: 10.2147/HP.S195827
pii: 195827
pmc: PMC6667353
doi:
Types de publication
Journal Article
Langues
eng
Pagination
41-52Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
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