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IRTKS promotes osteogenic differentiation by inhibiting PTEN phosphorylation.
- Source :
-
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 Aug; Vol. 177, pp. 116872. Date of Electronic Publication: 2024 Jun 21. - Publication Year :
- 2024
-
Abstract
- Insulin stimulates osteoblast proliferation and differentiation as an anabolic agent in bone. Insulin Receptor Tyrosine Kinase Substrate (IRTKS) is involved in insulin signaling as an adapter for insulin receptors (IR). Here, we showed that IRTKS levels were significantly decreased in bone marrow mesenchymal stem cells (BMSCs) derived from the bone marrow of patients with osteoporosis. Based on relevant experiments, we observed that IRTKS promoted the proliferation, migration, and osteoblast differentiation of BMSCs and MC3T3-E1 cells. In addition, we identified a Phosphatase and Tensin homolog deleted on chromosome 10 (PTEN) as a potential active substrate of IRTKS. We demonstrated a direct interaction between IRTKS and PTEN using co-immunoprecipitation. Subsequently, we confirmed that the SH3 domain of IRTKS directly binds to the C-terminal tail of PTEN. Further experimental results demonstrated that PTEN attenuated the promoting effects of IRTKS on the proliferation, migration, and osteoblast differentiation of BMSCs and MC3T3-E1 cells. In conclusion, this study suggests that IRTKS contributes to osteogenic differentiation by inhibiting PTEN phosphorylation and provides a potential therapeutic target for osteoporosis patients.<br />Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
- Subjects :
- Phosphorylation
Animals
Mice
Humans
Cell Movement
Insulin Receptor Substrate Proteins metabolism
Osteoporosis metabolism
Osteoporosis pathology
Cell Line
Female
PTEN Phosphohydrolase metabolism
PTEN Phosphohydrolase genetics
Osteogenesis
Cell Differentiation
Mesenchymal Stem Cells metabolism
Cell Proliferation
Osteoblasts metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1950-6007
- Volume :
- 177
- Database :
- MEDLINE
- Journal :
- Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
- Publication Type :
- Academic Journal
- Accession number :
- 38908202
- Full Text :
- https://doi.org/10.1016/j.biopha.2024.116872