Interleukin-6 induces the lineage commitment of bone marrow-derived mesenchymal multipotent cells through down-regulation of Sox2 by osteogenic transcription factors.
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.
Department of Orthopaedic Surgery, Yonsei University College of Medicine, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
Dong Suk
DS
Yoon
Department of Orthopaedic Surgery, Yonsei University College of Medicine, and.
Yun Hee
YH
Kim
Department of Orthopaedic Surgery, Yonsei University College of Medicine, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
Seulgi
S
Lee
Department of Orthopaedic Surgery, Yonsei University College of Medicine, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
Kyoung-Mi
KM
Lee
Department of Orthopaedic Surgery, Yonsei University College of Medicine, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea.
Kwang Hwan
KH
Park
Department of Orthopaedic Surgery, Yonsei University College of Medicine, and.
Yeonsue
Y
Jang
Department of Orthopaedic Surgery, Yonsei University College of Medicine, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, South Korea ljwos@yuhs.ac.
Jin Woo
JW
Lee
D000328:Adult; D001853:Bone Marrow / Q000378:metabolism*; D002450:Cell Communication / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019070:Cell Lineage / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics*; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D039902:Multipotent Stem Cells / Q000378:metabolism*; D010012:Osteogenesis / Q000235:genetics*; D055748:SOXB1 Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D055815:Young Adult
D050659:Core Binding Factor Alpha 1 Subunit; D016207:Cytokines; C100596:DLX5 protein, human; D018398:Homeodomain Proteins; C508600:IL6 protein, human; D015850:Interleukin-6; C493709:RUNX2 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D014157:Transcription Factors
Dlx5; Runx2; cell-cell interaction; heterogeneous population; stemness