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Interleukin-6 induces the lineage commitment of bone marrow-derived mesenchymal multipotent cells through down-regulation of Sox2 by osteogenic transcription factors

 Dong Suk Yoon  ;  Yun Hee Kim  ;  Seulgi Lee  ;  Kyoung-Mi Lee  ;  Kwang Hwan Park  ;  Yeonsue Jang  ;  Jin Woo Lee 
 FASEB JOURNAL, Vol.28(7) : 3273-3286, 2014 
Journal Title
Issue Date
Adult ; Bone Marrow/metabolism* ; Cell Communication/genetics ; Cell Differentiation/genetics ; Cell Lineage/genetics* ; Cellular Senescence/genetics ; Core Binding Factor Alpha 1 Subunit/genetics ; Core Binding Factor Alpha 1 Subunit/metabolism ; Cytokines/genetics ; Cytokines/metabolism ; Down-Regulation/genetics* ; Female ; Homeodomain Proteins/genetics ; Homeodomain Proteins/metabolism ; Humans ; Interleukin-6/genetics ; Interleukin-6/metabolism* ; Male ; Middle Aged ; Multipotent Stem Cells/metabolism* ; Osteogenesis/genetics* ; SOXB1 Transcription Factors/genetics* ; SOXB1 Transcription Factors/metabolism ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcription, Genetic/genetics ; Up-Regulation/genetics ; Young Adult
Dlx5 ; Runx2 ; cell-cell interaction ; heterogeneous population ; stemness
Bone marrow-derived mesenchymal stromal cells (BM-MSCs) are a heterogeneous population of cells that differ in size and morphology. BM-MSCs become committed to the osteogenic lineage as senescence approaches and lose multipotency. Nevertheless, little is known about the effects of cell-cell interaction between different populations on stemness loss and lineage commitment. The current study aimed to identify mechanisms by which cell-cell interactions between heterogeneous BM-MSCs affect stemness and lineage commitment of multipotent subpopulation. The lineage commitment of primitive multipotent cells was strongly induced in the presence of cytokines secreted by senescent-like cells in a cell culture insert system. Senescent-like cells secreted higher levels of interleukin-6 (IL-6) than primitive multipotent cells in a human cytokine array. IL-6 induced the lineage commitment and stemness loss in multipotent cells by decreasing Sox2 expression. Furthermore, we confirmed that IL-6 decreased the transcriptional activity of Sox2 through up-regulation of Runx2 and Dlx5. We suggest a mechanism by which IL-6 modulates the expression of Sox2, resulting in decreased multipotency and causing primitive multipotent cells to undergo osteogenic lineage commitment. This is the first study to identify mechanisms in which the cell-cell interactions between the different populations play important roles in the stemness loss and lineage commitment of multipotent populations.-Yoon, D. S., Kim, Y. H., Lee, S., Lee, K.-M., Park, K. H., Jang, Y., Lee, J. W. Interleukin-6 induces the lineage commitment of bone marrow-derived mesenchymal multipotent cells through down-regulation of Sox2 by osteogenic transcription factors.
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1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Orthopedic Surgery (정형외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
Yonsei Authors
Park, Kwang Hwan(박광환) ORCID logo https://orcid.org/0000-0002-2110-0559
Yoon, Dong Suk(윤동석) ORCID logo https://orcid.org/0000-0001-5945-5569
Lee, Kyoung Mi(이경미) ORCID logo https://orcid.org/0000-0002-9038-8162
Lee, Seul Gi(이슬기)
Lee, Jin Woo(이진우) ORCID logo https://orcid.org/0000-0002-0293-9017
Jang, Yeon Sue(장연수) ORCID logo https://orcid.org/0000-0001-5683-0001
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