Peripheral blood mononuclear phagocytes from patients with chronic periodontitis are primed for osteoclast formation.
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-α and higher amounts of interferon-γ, interleukin (IL)-1α, IL-1β, IL-1rα, CXC motif chemokine 10, macrophage migration inhibitory factor, macrophage inflammatory protein (MIP)-1α, and MIP-1β 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.
Departments of Physiology and Pathology, Araraquara Dental School, State University of São Paulo, Araraquara, Brazil.
Bruno S
BS
Herrera
Alliny S
AS
Bastos
Leila S
LS
Coimbra
Simone A
SA
Teixeira
Carlos
C
Rossa
Thomas E
TE
Van Dyke
Marcelo N
MN
Muscara
Luis C
LC
Spolidorio
D000135:Acid Phosphatase / Q000032:analysis; D000328:Adult; D001862:Bone Resorption / Q000473:pathology; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D054405:Chemokine CCL3 / Q000032:analysis; D054407:Chemokine CCL4 / Q000032:analysis; D054357:Chemokine CXCL10 / Q000032:analysis; D055113:Chronic Periodontitis / Q000097:blood* / Q000473:pathology; D006801:Humans; D007371:Interferon-gamma / Q000032:analysis; D053590:Interleukin 1 Receptor Antagonist Protein / Q000032:analysis; D053582:Interleukin-1alpha / Q000032:analysis; D053583:Interleukin-1beta / Q000032:analysis; D007527:Isoenzymes / Q000032:analysis; D018950:Lipopolysaccharide Receptors / Q000032:analysis; D008070:Lipopolysaccharides / Q000494:pharmacology; D016173:Macrophage Colony-Stimulating Factor / Q000097:blood / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000032:analysis; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology*; D010586:Phagocytes / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D053245:RANK Ligand / Q000494:pharmacology; D000071681:Tartrate-Resistant Acid Phosphatase; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
C515429:CCL3 protein, human; C066507:CCL4 protein, human; C114753:CXCL10 protein, human; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D054357:Chemokine CXCL10; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D007527:Isoenzymes; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008263:Macrophage Migration-Inhibitory Factors; D053245:RANK Ligand; C505688:TNFSF11 protein, human; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase