In vitro evaluation of the biological effect of SOFAT on osteoblasts

Author(s)

Napimoga, Marcelo Henrique ^[1] ; Dias Demasi, Ana Paula ^[2] ; Jarry, Christian Rado ^[3] ; Ortega, Mauricio Cardoso ^[3] ; de Araujo, Vera Cavalcanti ^[2] ; Martinez, Elizabeth Ferreira ^[2]

Affiliation

^[1] Sao Leopoldo Mand Inst & Res Ctr, Lab Immunol & Mol Biol, BR-13045755 Campinas, SP - Brazil

^[2] Sao Leopoldo Mand Inst & Res Ctr, Lab Oral Pathol, Campinas, SP - Brazil

^[3] Sao Leopoldo Mand Inst & Res Ctr, Dept Periodontol, Periodontal Med Res Grp, BR-13045755 Campinas, SP - Brazil

• Document type: Journal article
• Source: International Immunopharmacology; v. 26, n. 2, p. 378-383, JUN 2015.
• Web of Science Citations: 5

Abstract

Osteoclastogenesis is regulated by osteoblasts especially through the production of receptor activator of nuclear factor kappa-B ligand (RANKL). Immune cells present in inflamed tissues markedly increase this process by upregulating RANKL directly or by secreting proinflammatoly cytokines, which stimulate RANKL expression by osteoblasts. A novel T-cell-secreted cytokine, termed secreted osteoclastogenic factor of activated T cells (SOFAT) was recently described. To better understand how SOFAT affects bone metabolism, we investigated its effect on osteoblastic cells. We demonstrate here that SOFAT did not influence MC3T3 cells viability and proliferation, evaluated by trypan blue exclusion and MU tests, respectively. SOFAT stimulated the secretion of IL-6, IL-10 and GM-CSF in MOT3 cells, as shown by the analysis of an inflammatory cytokines ELISA array. The upregulation of the corresponding genes was checked by qPCR. Both RANKL mRNA and protein levels did not significantly change in the presence of SOFAT, evaluated by qPCR and western blotting, respectively. In addition, analysis of a PCR array for IL6/STAT3 pathway demonstrated that SOFAT induced the expression of BCl2, IL1B, IL10, IL22, IL2RA, IL4, IL6, TNFSF10 and PLAS3, while IL2, IL21, CD4, CSF3R and TNF were repressed. Our results confirm that the SOFAT mechanism of action is RANKL-independent and indicate that, by co-opting osteoblasts to increase the production of osteoclastogenic cytolcines, SOFAT may exacerbate inflammation and support osteoclast formation and bone destruction. (C) 2015 Elsevier B.V. All rights reserved. (AU)

• FAPESP's process: 13/09524-2 - Evaluation of the effects of the cytokine SOFAT on osteoblast cells and its potential on bone inflammatory diseases
• Grantee: Marcelo Henrique Napimoga
• Support Opportunities: Regular Research Grants