Mesenchymal stromal cell-derived septoclasts resorb cartilage during developmental ossification and fracture healing.
Animals
Bone and Bones
/ cytology
Cartilage
/ cytology
Cells, Cultured
Chondrocytes
/ cytology
Fatty Acid-Binding Proteins
/ genetics
Female
Fracture Healing
/ genetics
Humans
Male
Mesenchymal Stem Cells
/ cytology
Mice, Inbred C57BL
Mice, Knockout
Mice, Transgenic
Microscopy, Immunoelectron
Neoplasm Proteins
/ genetics
Osteoclasts
/ cytology
Osteogenesis
/ genetics
RNA-Seq
/ methods
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
28 01 2022
28 01 2022
Historique:
received:
28
09
2020
accepted:
11
01
2022
entrez:
29
1
2022
pubmed:
30
1
2022
medline:
24
2
2022
Statut:
epublish
Résumé
Developmental osteogenesis, physiological bone remodelling and fracture healing require removal of matrix and cellular debris. Osteoclasts generated by the fusion of circulating monocytes degrade bone, whereas the identity of the cells responsible for cartilage resorption is a long-standing and controversial question. Here we show that matrix degradation and chondrocyte phagocytosis are mediated by fatty acid binding protein 5-expressing cells representing septoclasts, which have a mesenchymal origin and are not derived from haematopoietic cells. The Notch ligand Delta-like 4, provided by endothelial cells, is necessary for septoclast specification and developmental bone growth. Consistent with the termination of growth, septoclasts disappear in adult and ageing bone, but re-emerge in association with growing vessels during fracture healing. We propose that cartilage degradation is mediated by rare, specialized cells distinct from osteoclasts. Our findings have implications for fracture healing, which is frequently impaired in aging humans.
Identifiants
pubmed: 35091558
doi: 10.1038/s41467-022-28142-w
pii: 10.1038/s41467-022-28142-w
pmc: PMC8799643
doi:
Substances chimiques
Fabp5 protein, mouse
0
Fatty Acid-Binding Proteins
0
Neoplasm Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
571Informations de copyright
© 2022. The Author(s).
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