Macrophage metabolism directs regenerative versus fibrotic healing through BMP signaling in the mouse digit tip
Rattachement africain : us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
Macrophages play a central role in determining the outcomes of healing, coordinating regeneration in some injuries and scar formation in others. In both cases, this coordination involves the cross-talk between macrophages and surrounding cells. But what drives the different cross-communication pathways to determine healing outcomes is not well known. In this study, we make use of the mouse digit tip amputation model, in which an amputation through the third phalangeal element (P3) is able to completely regenerate whereas an amputation through the second phalangeal element (P2) forms a scar. We identify a population of macrophages that is specific to the P3 regenerating digit. By integrating single-cell RNAseq, spatial transcriptomics, and metabolomic analyses, we show that this population localizes specifically to the growing bone front, express BMP ligands that drive downstream BMP activation in neighboring osteoblasts and is governed by a two-part metabolic switch involving increased fatty acid oxidation coupled with reduced glycolytic activity. This spatially restricted, BMP-expressing macrophage population is entirely absent in the scar-forming P2 injury, and our data indicate that environmental conditions unique to the regenerating digit are responsible for its emergence. Together these findings identify a regeneration-specific macrophage signaling center for patterned bone formation and suggest that targeting the metabolic conditions that drive this population could improve the efficacy of regenerative therapies.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.
Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Macrophage metabolism directs regenerative versus fibrotic healing through BMP signaling in the mouse digit tip
- Date Crossref
- 07/05/2026
- Éditeur
- openRxiv
- Type
- posted-content
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
-
Mayo Clinic in Arizona Department of Orthopedic Surgery pays non établi dans la noticeÉtablissement de santé
-
University of Kentucky Department of Microbiology pays non établi dans la noticeUniversité ou école supérieure
-
Louisiana State University Health Sciences Center New Orleans Department of Orthopedic Surgery pays non établi dans la noticeÉtablissement de santé
-
The University of Texas Southwestern Medical Center Department of Surgery pays non établi dans la noticeÉtablissement de santé
-
Inc. Baltimore Gigantest pays non établi dans la noticeEntreprise
Department of Orthopedic Surgery — Mayo Clinic in Arizona, Department of Microbiology — University of Kentucky et Department of Orthopedic Surgery — Louisiana State University Health Sciences Center New Orleans, avec 2 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.