| RRC ID |
69382
|
| 著者 |
Iwata T, Mizuno N, Ishida S, Kajiya M, Nagahara T, Kaneda-Ikeda E, Yoshioka M, Munenaga S, Ouhara K, Fujita T, Kawaguchi H, Kurihara H.
|
| タイトル |
Functional Regulatory Mechanisms Underlying Bone Marrow Mesenchymal Stem Cell Senescence During Cell Passages.
|
| ジャーナル |
Cell Biochem Biophys
|
| Abstract |
Mesenchymal stem cell (MSC) transplantation is an effective periodontal regenerative therapy. MSCs are multipotent, have self-renewal ability, and can differentiate into periodontal cells. However, senescence is inevitable for MSCs. In vitro, cell senescence can be induced by long-term culture with/without cell passage. However, the regulatory mechanism of MSC senescence remains unclear. Undifferentiated MSC-specific transcription factors can regulate MSC function. Herein, we identified the regulatory transcription factors involved in MSC senescence and elucidated their mechanisms of action. We cultured human MSCs (hMSCs) with repetitive cell passages to induce cell senescence and evaluated the mRNA and protein expression of cell senescence-related genes. Additionally, we silenced the cell senescence-induced transcription factors, GATA binding protein 6 (GATA6) and SRY-box 11 (SOX11), and investigated senescence-related signaling pathways. With repeated passages, the number of senescent cells increased, while the cell proliferation capacity decreased; GATA6 mRNA expression was upregulated and that of SOX11 was downregulated. Repetitive cell passages decreased Wnt and bone morphogenetic protein (BMP) signaling pathway-related gene expression. Silencing of GATA6 and SOX11 regulated Wnt and BMP signaling pathway-related genes and affected cell senescence-related genes; moreover, SOX11 silencing regulated GATA6 expression. Hence, we identified them as pair of regulatory transcription factors for cell senescence in hMSCs via the Wnt and BMP signaling pathways.
|
| 巻・号 |
79(2)
|
| ページ |
321-336
|
| 公開日 |
2021-6-1
|
| DOI |
10.1007/s12013-021-00969-y
|
| PII |
10.1007/s12013-021-00969-y
|
| PMID |
33559812
|
| MeSH |
Bone Marrow Cells / cytology
Bone Morphogenetic Proteins / genetics
Bone Morphogenetic Proteins / metabolism
Cell Differentiation
Cell Proliferation
Cells, Cultured
Cellular Senescence / genetics*
GATA6 Transcription Factor / antagonists & inhibitors
GATA6 Transcription Factor / genetics
GATA6 Transcription Factor / metabolism
Histone Deacetylase 2 / genetics
Histone Deacetylase 2 / metabolism
Humans
Mesenchymal Stem Cells / cytology
Mesenchymal Stem Cells / metabolism
RNA Interference
RNA, Small Interfering / metabolism
SOXC Transcription Factors / antagonists & inhibitors
SOXC Transcription Factors / genetics
SOXC Transcription Factors / metabolism
Signal Transduction / genetics
Wnt Proteins / genetics
Wnt Proteins / metabolism
|
| IF |
2.073
|
| リソース情報 |
| ヒト・動物細胞 |
human mesenchymal stem cell |
