Down-regulation of expression of osteoblast and osteocyte markers in periodontal tissues associated with the spontaneous alveolar bone loss of interleukin-10 knockout mice.

The aim of this study was to unravel the mechanisms by which interleukin (IL)-10, a potent pleiotropic cytokine, modulates alveolar bone homeostasis in C57BL/6 wild-type (WT) and IL-10 knockout (IL-10 KO) mice, evaluated at 8, 24, and 48 wk of age. Interleukin-10 KO mice presented significant alveolar bone loss when compared with WT mice, and this was not associated with changes in leukocyte counts or bacterial load. The levels of expression of messenger RNA (mRNA) for tumor necrosis factor-alpha (TNF-alpha), IL-1beta, IL-6, transforming growth factor-beta (TGF-beta), receptor activator of nuclear factor kappaB ligand (RANKL), osteoprotegerin (OPG), and matrix metalloproteinase 13 (MMP13) were similar between both strains, whereas a significant decrease of tissue inhibitor of metalloproteinase 1 (TIMP1) mRNA expression was found at 48 wk in IL-10 KO mice. The osteoblast markers core binding factor alpha1 (CBFA1) and type I collagen (COL-I) were expressed at similar levels in both strains, whereas the levels of alkaline phosphatase (ALP) and osteocalcin (OCN), and those of the osteocyte markers phosphate-regulating gene endopeptidases (PHEX) and dentin matrix protein 1 (DMP1) were significantly lower in IL-10 KO mice. Our results demonstrate that the alveolar bone loss in the absence of IL-10 was associated with a reduced expression of osteoblast and osteocyte markers, an effect independent of microbial, inflammatory or bone-resorptive pathways.

The essential role of IFN-gamma in the control of lethal Aggregatibacter actinomycetemcomitans infection in mice.

Inflammatory immune reactions in response to periodontopathogens trigger periodontal destruction, but their role to protect the host against infection remains unknown. Thus, we examined the mechanisms by which IFN-gamma modulates the outcome of Aggregatibacter actinomycetemcomitans-induced periodontal disease in mice. Our results showed that IFN-gamma deficient mice developed less severe periodontitis in response to A. actinomycetemcomitans infection, characterized by significant lower alveolar bone loss and inflammatory reaction. However, the absence of IFN-gamma results in increased bacterial load in periodontal tissues and higher acute phase reaction, followed by a disseminated bacterial infection and mice death during the course of the disease. Such impaired host response was found to be associated with a reduction in the levels of inflammatory cytokines and chemokines and in the number of GR1+, F4/80+, CD4+ and CD8+ leukocytes in the diseased periodontium of IFN-gamma deficient mice. In addition, the levels of both antimicrobial mediators myeloperoxidase and inducible nitric oxide synthase were also found to be reduced in IFN-KO mice. Our results demonstrate for the first time that a periodontal infection may be lethal in an immunocompromised host. In addition, the mechanisms involved in IFN-gamma mediated cell migration to diseased periodontal tissues, and its essential role to control A. actinomycetemcomitans infection were clarified.

Cytokine expression pattern in compression and tension sides of the periodontal ligament during orthodontic tooth movement in humans.

Orthodontic tooth movement is achieved by the remodeling of periodontal ligament (PDL) and alveolar bone in response to mechanical loading and is believed to be mediated by several host mediators, such as cytokines. By means of real-time polymerase chain reaction (PCR), we studied the pattern of expression of mRNA encoding several pro- and anti-inflammatory cytokines in relation to several extracellular matrix and bone remodeling markers, in tension (T) and compression (C) sides of the PDL of human teeth subjected to rapid maxillary expansion. The PDL of normal teeth was used as a control. The results showed that both T and C sides exhibited significantly higher expression of all targets when compared with controls, except for type I collagen (COL-I) and tissue inhibitor of metalloproteinase-1 (TIMP-1) on the C side. Comparing C and T sides, the C side exhibited higher expression of tumor necrosis factor-alpha (TNF-alpha), receptor activator of nuclear factor-kappaB ligand (RANKL), and matrix metalloproteinase-1 (MMP-1), whereas the T side presented higher expression of interleukin-10 (IL-10), TIMP-1, COL-I, osteoprotegerin (OPG), and osteocalcin (OCN). The expression of transforming growth factor-beta (TGF-beta) was similar in both C and T sides. Our data demonstrate a differential expression of pro- and anti-inflammatory cytokines in compressed and stretched PDL during orthodontic tooth movement.