Herrera, Bruno S.
[1, 2, 3]
Bastos, Alliny S.
Coimbra, Leila S.
Teixeira, Simone A.
Rossa, Jr., Carlos
Van Dyke, Thomas E.
Muscara, Marcelo N.
Spolidorio, Luis C.
Total Authors: 8
 State Univ Sao Paulo, Araraquara Dent Sch, Dept Physiol, Araraquara - Brazil
 State Univ Sao Paulo, Araraquara Dent Sch, Dept Pathol, Araraquara - Brazil
 Forsyth Inst, Dept Appl Oral Sci, Cambridge, MA 02142 - USA
 State Univ Sao Paulo, Araraquara Dent Sch, Dept Diag, Araraquara - Brazil
 State Univ Sao Paulo, Araraquara Dent Sch, Dept Surg, Araraquara - Brazil
 Univ Sao Paulo, Inst Biomed Sci, Dept Pharmacol, Sao Paulo - Brazil
Total Affiliations: 6
Journal of Periodontology;
Web of Science Citations:
Background: During inflammatory periodontal disease, peripheral blood mononuclear cells (PBMCs) are attracted to bone and differentiate into active bone-resorbing osteoclasts (OCs), thus providing evidence that the impact of chronic periodontitis (CP) on the activity of circulating mononuclear cells is of central importance. The authors test the hypothesis that peripheral blood mononuclear phagocytes (PBMPs) from patients with CP are activated and more susceptible to differentiation into OCs, which in turn would lead to more intense bone resorption. Methods: In vitro cytokine production by both unstimulated and lipopolysaccharide-stimulated PBMCs from individuals with (n = 10) or without (n = 12) periodontitis was determined by cytokine array. OC differentiation from CD14(+) PBMCs was induced by receptor activator of nuclear factor-kappa B ligand (RANKL), either alone or in the presence of macrophage colony-stimulating factor (M-CSF). PBMC differentiation to OCs was confirmed by tartrate-resistant acid phosphatase staining; bone resorbing activity was assessed by using an osteologic plate assay (bone resorption pit formation). Results: PBMCs from patients with CP produced tumor necrosis factor-a and higher amounts of interferon-gamma, interleukin (IL)-1 alpha, IL-1 beta, IL-1r alpha, CXC motif chemokine 10, macrophage migration inhibitory factor, macrophage inflammatory protein (MIP)-1 alpha, and MIP-1 beta than the control cells. OC differentiation was induced by RANKL alone in PBMCs from patients with CP, but not in PBMCs from the healthy controls, which required the addition of M-CSF. In addition, PBMC-derived OCs from patients with CP showed significantly higher resorption activity than that observed in the healthy controls. Also, the circulating concentrations of M-CSF were significantly higher in patients with CP than in the control participants. Conclusions: These data indicate that in patients with CP, circulating PBMCs are primed for increased proinflammatory activity and that M-CSF plays a central role in this process by increasing OC formation and the consequent bone resorption activity. (AU)