Cardiotrophin-like cytokine (CLCF1) modulates mesenchymal stem cell osteoblastic differentiation

Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into adipocytes, chondrocytes, or osteocytes. MSCs secrete an array of cytokines and express the LIFRβ (leukemia inhibitory factor receptor) chain on their surface. Mutations in the gene coding for LIFRβ lead to a syndrom...

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Bibliographic Details
Published in:The Journal of biological chemistry 2019-08, Vol.294 (32), p.11952-11959
Main Authors: Nahlé, Sarah, Pasquin, Sarah, Laplante, Véronique, Rousseau, François, Sharma, Mukut, Gauchat, Jean-François
Format: Article
Language:English
Subjects:
Accelerated Communications
Animals
bone
Bone Marrow Cells - cytology
cardiotrophin-like cytokine (CLCF1)
Cell Differentiation
Cells, Cultured
cytokine
Cytokines - genetics
Cytokines - metabolism
mesenchymal stem cells (MSCs)
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Mice
Mice, Inbred C57BL
Mutagenesis
osteoblast
Osteoblasts - cytology
Osteoblasts - metabolism
Osteogenesis
osteoporosis
Phosphorylation
Signal Transduction
STAT1 Transcription Factor - metabolism
STAT3 Transcription Factor - metabolism
Up-Regulation
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Summary:Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into adipocytes, chondrocytes, or osteocytes. MSCs secrete an array of cytokines and express the LIFRβ (leukemia inhibitory factor receptor) chain on their surface. Mutations in the gene coding for LIFRβ lead to a syndrome with altered bone metabolism. LIFRβ is one of the signaling receptor chains for cardiotrophin-like cytokine (CLCF1), a neurotrophic factor known to modulate B and myeloid cell functions. We investigated its effect on MSCs induced to differentiate into osteocytes in vitro. Our results indicate that CLCF1 binds mouse MSCs, triggers STAT1 and -3 phosphorylation, inhibits the up-regulation of master genes involved in the control of osteogenesis, and markedly prevents osteoblast generation and mineralization. This suggests that CLCF1 could be a target for therapeutic intervention with agents such as cytokine traps or blocking mAbs in bone diseases such as osteoporosis.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.AC119.008361