Monocytes differentiation upon treatment with a peptide corresponding to the C-terminus of activated T cell-expressed Tirc7 protein.
Atp6v0a3 gene encodes for two alternative products, Tirc7 and a3 proteins, which are differentially expressed in activated T cells and resorbing osteoclasts, respectively. Tirc7 plays a central role in T cell activation, while a3 protein is critical for osteoclast-mediated bone matrix resorption. Based on the large body of evidences documenting the relationships between T cells and osteoclasts, we hypothesized that the extracellular C-terminus of Tirc7 protein could directly interact with osteoclast precursor cells. To address this issue, we performed the molecular cloning of a mouse Atp6v0a3 cDNA segment encoding the last 40 amino acids of Tirc7 protein, and we used this peptide as a ligand added to mouse osteoclast precursor cells. We evidenced that Tirc7-Cter peptide induced the differentiation of RAW264.7 cells into osteoclast-like cells, stimulated an autocrine/paracrine regulatory loop potentially involved in osteoclastic differentiation control, and strongly up-regulated F4/80 protein expression within multinucleated osteoclast-like cells. Using a mouse bone marrow-derived CD11b(+) cell line, or total bone marrow primary cells, we observed that similarly to Rankl, Tirc7-Cter peptide induced the formation of TRACP-positive large multinucleated cells. At last, using mouse primary monocytes purified from total bone marrow, we determined that Tirc7-Cter peptide induced the appearance of small multinucleated cells (3-4 nuclei), devoid of resorbing activity, and which displayed modulations of dendritic cell marker genes expression. In conclusion, we report for the first time on biological effects mediated by a peptide corresponding to the C-terminus of Tirc7 protein, which interfere with monocytic differentiation pathways.
GéPITOs, Université de Nice, CNRS, UMR 6235, UFR Médecine, NICE, Cedex 2, France.
Caroline C
CC
Mouline
Guillaume E
GE
Beranger
Heidy
H
Schmid-Antomarchi
Danielle
D
Quincey
David
D
Momier
Florian
F
Boukhechba
Georges F
GF
Carle
Nathalie
N
Rochet
Jean-Claude
JC
Scimeca
D000818:Animals; D001853:Bone Marrow; D002454:Cell Differentiation; D051379:Mice; D009000:Monocytes / Q000166:cytology; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D025262:Vacuolar Proton-Translocating ATPases / Q000235:genetics* / Q000378:metabolism
C484226:Atp6ap1 protein, mouse; D010455:Peptides; D025262:Vacuolar Proton-Translocating ATPases