RRC ID 69382
Author 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.
Title Functional Regulatory Mechanisms Underlying Bone Marrow Mesenchymal Stem Cell Senescence During Cell Passages.
Journal 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.
Volume 79(2)
Pages 321-336
Published 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
Human and Animal Cells human mesenchymal stem cell