Microcomputed tomography staging of bone histolysis in the regenerating mouse digit.
Blastema
digit
intramembranous ossification
osteoclasts
regeneration
Journal
Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society
ISSN: 1524-475X
Titre abrégé: Wound Repair Regen
Pays: United States
ID NLM: 9310939
Informations de publication
Date de publication:
Jan 2023
Jan 2023
Historique:
revised:
10
08
2022
received:
06
06
2022
accepted:
14
09
2022
pubmed:
1
10
2022
medline:
25
1
2023
entrez:
30
9
2022
Statut:
ppublish
Résumé
Humans and mice have the ability to regenerate the distal digit tip, the terminal phalanx (P3) in response to amputation. What distinguishes P3 regeneration from regenerative failure is formation of the blastema, a proliferative structure that undergoes morphogenesis to regenerate the amputated tissues. P3 regeneration is characterised by the phases of inflammation, tissue histolysis and expansive bone degradation with simultaneous blastema formation, wound closure and finally blastemal differentiation to restore the amputated structures. While each regenerating digit faithfully progresses through all phases of regeneration, phase progression has traditionally been delineated by time, that is, days postamputation (DPA), yet there is widespread variability in the timing of the individual phases. To diminish variability between digits during tissue histolysis and blastema formation, we have established an in-vivo method using microcomputed tomography (micro CT) scanning to identify five distinct stages of the early regeneration response based on anatomical changes of the digit stump. We report that categorising the initial phases of digit regeneration by stage rather than time greatly diminishes the variability between digits with respect to changes in bone volume and length. Also, stages correlate with the levels of cell proliferation, osteoclast recruitment and osteoprogenitor cell recruitment. Importantly, micro CT staging provides a means to estimate open versus closed digit wounds. We demonstrate two spatially distinct and stage specific bone repair/regeneration responses that occur during P3 regeneration. Collectively, these studies showcase the utility of micro CT imaging to infer the composition of radiolucent soft tissues during P3 blastema formation. Specifically, the staging system identifies the onset of cell proliferation, osteoclastogenesis, osteoprogenitor recruitment, the spatial initiation of de novo bone formation and epidermal closure.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
17-27Subventions
Organisme : NICHD NIH HHS
ID : F31 HD110287
Pays : United States
Informations de copyright
© 2022 The Wound Healing Society.
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