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Transforming Growth Factor-β1 (TGF-β1) Induces Mouse Precartilaginous Stem Cell Proliferation through TGF-β Receptor II (TGFRII)-Akt-β-Catenin Signaling
Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We s...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4139866/ https://www.ncbi.nlm.nih.gov/pubmed/25036031 http://dx.doi.org/10.3390/ijms150712665 |
Sumario: | Precartilaginous stem cells (PSCs) could self-renew or differentiate into chondrocytes to promote bone growth. In the current study, we aim to understand the role of transforming growth factor-β1 (TGF-β1) in precartilaginous stem cell (PSC) proliferation, and to study the underlying mechanisms. We successfully purified and primary-cultured PSCs from the neonate mice’ perichondrial mesenchyme, and their phenotype was confirmed by the PSC marker fibroblast growth factor receptor-3 (FGFR-3) overexpression. We found that TGF-β1 induced Akt-glycogen synthase kinase-3β (GSK3β) phosphorylation and β-catenin nuclear translocation in the mouse PSCs, which was almost blocked by TGF-β receptor-II (TGFRII) shRNA knockdown. Further, perifosine and MK-2206, two Akt-specific inhibitors, suppressed TGF-β1-induced GSK3β phosphorylation and β-catenin nuclear translocation. Akt inhibitors, as well as β-catenin shRNA knockdown largely inhibited TGF-β1-stimulated cyclin D1/c-myc gene transcription and mouse PSC proliferation. Based on these results, we suggest that TGF-β1 induces Akt activation to promote β-catenin nuclear accumulation, which then regulates cyclin D1/c-myc gene transcription to eventually promote mouse PSC proliferation. |
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