Ror2 signaling regulated by differential Wnt proteins determines pathological fate of muscle mesenchymal progenitors.
Receptor Tyrosine Kinase-like Orphan Receptors
/ metabolism
Animals
Mesenchymal Stem Cells
/ metabolism
Mice
Muscle, Skeletal
/ metabolism
Wnt Proteins
/ metabolism
Cell Proliferation
Humans
Mice, Inbred C57BL
Signal Transduction
Adipose Tissue
/ metabolism
Cell Differentiation
Wnt Signaling Pathway
Journal
Cell death & disease
ISSN: 2041-4889
Titre abrégé: Cell Death Dis
Pays: England
ID NLM: 101524092
Informations de publication
Date de publication:
29 Oct 2024
29 Oct 2024
Historique:
received:
02
07
2024
accepted:
21
10
2024
revised:
18
10
2024
medline:
29
10
2024
pubmed:
29
10
2024
entrez:
29
10
2024
Statut:
epublish
Résumé
Skeletal muscle mesenchymal progenitors (MPs) play a critical role in supporting muscle regeneration. However, under pathological conditions, they contribute to intramuscular adipose tissue accumulation, involved in muscle diseases, including muscular dystrophy and sarcopenia, age-related muscular atrophy. How MP fate is determined in these different contexts remains unelucidated. Here, we report that Ror2, a non-canonical Wnt signaling receptor, is selectively expressed in MPs and regulates their pathological features in a differential ligand-dependent manner. We identified Wnt11 and Wnt5b as ligands of Ror2. In vitro, Wnt11 inhibited MP senescence, which is required for normal muscle regeneration, and Wnt5b promoted MP proliferation. We further found that both Wnts are abundant in degenerating muscle and synergistically stimulate Ror2, leading to unwanted MP proliferation and eventually intramuscular adipose tissue accumulation. These findings provide evidence that Ror2-mediated signaling elicited by differential Wnts plays a critical role in determining the pathological fate of MPs.
Identifiants
pubmed: 39468010
doi: 10.1038/s41419-024-07173-9
pii: 10.1038/s41419-024-07173-9
doi:
Substances chimiques
Receptor Tyrosine Kinase-like Orphan Receptors
EC 2.7.10.1
Ror2 protein, mouse
EC 2.7.10.1
Wnt Proteins
0
ROR2 protein, human
EC 2.7.10.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
784Subventions
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP21gm1210005
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP21gm5010001
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : 19J10186
Organisme : MEXT | Japan Society for the Promotion of Science (JSPS)
ID : JP23H00456
Organisme : MEXT | JST | Precursory Research for Embryonic Science and Technology (PRESTO)
ID : JPMJPR2283
Informations de copyright
© 2024. The Author(s).
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