Mouse Digit Tip Regeneration Is Mechanical Load Dependent.
BLASTEMA
DE NOVO BONE FORMATION
DIGIT
HINDLIMB UNLOADING
MAMMALIAN REGENERATION
MECHANICAL UNLOADING
Journal
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
ISSN: 1523-4681
Titre abrégé: J Bone Miner Res
Pays: United States
ID NLM: 8610640
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
revised:
12
10
2021
received:
08
08
2021
accepted:
08
11
2021
pubmed:
17
11
2021
medline:
15
3
2022
entrez:
16
11
2021
Statut:
ppublish
Résumé
Amputation of the mouse digit tip results in blastema-mediated regeneration. In this model, new bone regenerates de novo to lengthen the amputated stump bone, resulting in a functional replacement of the terminal phalangeal element along with associated non-skeletal tissues. Physiological examples of bone repair, such as distraction osteogenesis and fracture repair, are well known to require mechanical loading. However, the role of mechanical loading during mammalian digit tip regeneration is unknown. In this study, we demonstrate that reducing mechanical loading inhibits blastema formation by attenuating bone resorption and wound closure, resulting in the complete inhibition of digit regeneration. Mechanical unloading effects on wound healing and regeneration are completely reversible when mechanical loading is restored. Mechanical unloading after blastema formation results in a reduced rate of de novo bone formation, demonstrating mechanical load dependence of the bone regenerative response. Moreover, enhancing the wound-healing response of mechanically unloaded digits with the cyanoacrylate tissue adhesive Dermabond improves wound closure and partially rescues digit tip regeneration. Taken together, these results demonstrate that mammalian digit tip regeneration is mechanical load-dependent. Given that human fingertip regeneration shares many characteristics with the mouse digit tip, these results identify mechanical load as a previously unappreciated requirement for de novo bone regeneration in humans. © 2021 American Society for Bone and Mineral Research (ASBMR).
Identifiants
pubmed: 34783092
doi: 10.1002/jbmr.4470
pmc: PMC9400037
mid: NIHMS1825156
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
312-322Subventions
Organisme : NICHD NIH HHS
ID : F31 HD110287
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD102909
Pays : United States
Informations de copyright
© 2021 American Society for Bone and Mineral Research (ASBMR).
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