Mechanical induction of osteoanabolic Wnt1 promotes osteoblast differentiation via Plat.
Wnt1 signaling
age-related osteoporosis
osteoblast differentiation
plasminogen activator
post-menopausal osteoporosis
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
29 Feb 2024
29 Feb 2024
Historique:
revised:
04
01
2024
received:
13
07
2023
accepted:
30
01
2024
medline:
26
2
2024
pubmed:
26
2
2024
entrez:
26
2
2024
Statut:
ppublish
Résumé
Physical activity-induced mechanical stimuli play a crucial role in preserving bone mass and structure by promoting bone formation. While the Wnt pathway is pivotal for mediating the osteoblast response to loading, the exact mechanisms are not fully understood. Here, we found that mechanical stimulation induces osteoblastic Wnt1 expression, resulting in an upregulation of key osteogenic marker genes, including Runx2 and Sp7, while Wnt1 knockdown using siRNA prevented these effects. RNAseq analysis identified Plat as a major target through which Wnt1 exerts its osteogenic influence. This was corroborated by Plat depletion using siRNA, confirming its positive role in osteogenic differentiation. Moreover, we demonstrated that mechanical stimulation enhances Plat expression, which, in turn leads to increased expression of osteogenic markers like Runx2 and Sp7. Notably, Plat depletion by siRNA prevented this effect. We have established that Wnt1 regulates Plat expression by activating β-Catenin. Silencing Wnt1 impairs mechanically induced β-Catenin activation, subsequently reducing Plat expression. Furthermore, our findings showed that Wnt1 is essential for osteoblasts to respond to mechanical stimulation and induce Runx2 and Sp7 expression, in part through the Wnt1/β-Catenin/Plat signaling pathway. Additionally, we observed significantly reduced Wnt1 and Plat expression in bones from ovariectomy (OVX)-induced and age-related osteoporotic mouse models compared with non-OVX and young mice, respectively. Overall, our data suggested that Wnt1 and Plat play significant roles in mechanically induced osteogenesis. Their decreased expression in bones from OVX and aged mice highlights their potential involvement in post-menopausal and age-related osteoporosis, respectively.
Identifiants
pubmed: 38407813
doi: 10.1096/fj.202301424RR
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e23489Subventions
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : 447674765
Organisme : Deutsche Forschungsgemeinschaft (DFG)
ID : IG18/21-1
Organisme : Robert Bosch Stiftung (RBS)
Organisme : UULM | Medizinische Fakultät, Universität Ulm (Medical schoo, Ulm University)
ID : L.SBN.0224
Informations de copyright
© 2024 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.
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