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J Biol Chem. 2019 Aug 9;294(32):11952-11959. doi: 10.1074/jbc.AC119.008361. Epub 2019 Jun 27.

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

Author information

1
Département de Pharmacologie et Physiologie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada.
2
Novimmune SA, 1228 Plan-Les-Ouates, Switzerland.
3
Renal Division, Kansas City Veterans Affairs Medical Center, Kansas City, Missouri 64128-2226.
4
Département de Pharmacologie et Physiologie, Université de Montréal, Montreal, Quebec H3T 1J4, Canada jf.gauchat@umontreal.ca.

Abstract

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.

KEYWORDS:

bone; cardiotrophin-like cytokine (CLCF1); cytokine; mesenchymal stem cells (MSCs); osteoblast; osteoporosis

PMID:
31248987
PMCID:
PMC6690685
[Available on 2020-08-09]
DOI:
10.1074/jbc.AC119.008361

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