Monocytes differentiation upon treatment with a peptide corresponding to the C-terminus of activated T cell-expressed Tirc7 protein

• Published in: Journal of cellular physiology 2012-08, Vol.227 (8), p.3088-3098
• Main Authors: Mouline, Caroline C., Beranger, Guillaume E., Schmid-Antomarchi, Heidy, Quincey, Danielle, Momier, David, Boukhechba, Florian, Carle, Georges F., Rochet, Nathalie, Scimeca, Jean-Claude
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry, Molecular Biology; Bone Marrow; Cell Differentiation; Life Sciences; Mice; Monocytes - cytology; Osteoclasts - cytology; Osteoclasts - metabolism; Peptides - genetics; Peptides - metabolism; Vacuolar Proton-Translocating ATPases - genetics; Vacuolar Proton-Translocating ATPases - metabolism
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.23059

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. J. Cell. Physiol. 227: 3088–3098, 2012. © 2011 Wiley Periodicals, Inc.