Linked Life Data

20191615

Source:http://linkedlifedata.com/resource/pubmed/id/20191615

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2010-4-8
pubmed:abstractText
Interleukin-34 (IL-34) is a newly discovered regulator of myeloid lineage differentiation, proliferation, and survival, acting via the macrophage-colony stimulating factor receptor (M-CSF receptor, c-fms). M-CSF, the main ligand for c-fms, is required for osteoclastogenesis and has been already identified as a critical contributor of the pathogenesis of giant cell tumours of bone (GCTs), tumours rich in osteoclasts. According to the key role of M-CSF in osteoclastogenesis and GCTs, the expression of IL-34 in human GCTs was first assessed. Quantitative analysis of IL-34 mRNA expression in 14 human GCTs revealed expression of this cytokine in GCTs as well as M-CSF and c-fms. Immunohistochemistry demonstrated that osteoclast-like cells exhibited a huge immunostaining for IL-34 and that mononuclear stromal cells were slightly positive for this protein. In contrast to osteoblasts, bone-resorbing osteoclasts showed very strong staining for IL-34, suggesting its potential role in the pathogenesis of GCTs by facilitating osteoclast formation. The role of IL-34 in osteoclastogenesis was then studied in murine and human models. IL-34 was able to support RANKL-induced osteoclastogenesis in the absence of M-CSF in all models. Multinucleated cells generated in the presence of IL-34 and RANKL expressed specific osteoclastic markers and resorbed dentine. IL-34 induced phosphorylation of ERK 1/2 and Akt through the activation of c-fms, as revealed by the inhibition of signalling by a specific c-fms tyrosine kinase inhibitor. Furthermore, IL-34 stimulated RANKL-induced osteoclastogenesis by promoting the adhesion and proliferation of osteoclast progenitors, and had no effect on osteoclast survival. Overall, these data reveal that IL-34 can be entirely substituted for M-CSF in RANKL-induced osteoclastogenesis, thus identifying a new biological activity for this cytokine and a contribution to the pathogenesis of GCTs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1096-9896
pubmed:author
pubmed:copyrightInfo
Copyright (c) 2010 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
pubmed:issnType
Electronic
pubmed:volume
221
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-86
pubmed:dateRevised
2011-2-7
pubmed:meshHeading
pubmed-meshheading:20191615-Adult, pubmed-meshheading:20191615-Aged, pubmed-meshheading:20191615-Animals, pubmed-meshheading:20191615-Anisoles, pubmed-meshheading:20191615-Antigens, CD11b, pubmed-meshheading:20191615-Bone Neoplasms, pubmed-meshheading:20191615-Bone Resorption, pubmed-meshheading:20191615-Carcinoma, Giant Cell, pubmed-meshheading:20191615-Cell Adhesion, pubmed-meshheading:20191615-Cell Proliferation, pubmed-meshheading:20191615-Cell Survival, pubmed-meshheading:20191615-Cells, Cultured, pubmed-meshheading:20191615-Dose-Response Relationship, Drug, pubmed-meshheading:20191615-Female, pubmed-meshheading:20191615-Humans, pubmed-meshheading:20191615-Interleukins, pubmed-meshheading:20191615-Male, pubmed-meshheading:20191615-Mice, pubmed-meshheading:20191615-Mice, Inbred C57BL, pubmed-meshheading:20191615-Middle Aged, pubmed-meshheading:20191615-Neoplasm Proteins, pubmed-meshheading:20191615-Osteoclasts, pubmed-meshheading:20191615-Pyrimidines, pubmed-meshheading:20191615-RANK Ligand, pubmed-meshheading:20191615-Receptor, Macrophage Colony-Stimulating Factor, pubmed-meshheading:20191615-Signal Transduction, pubmed-meshheading:20191615-Young Adult
pubmed:year
2010
pubmed:articleTitle
Interleukin-34 is expressed by giant cell tumours of bone and plays a key role in RANKL-induced osteoclastogenesis.
pubmed:affiliation
INSERM, UMR-S 957, Nantes F-44035, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't