A new method of measuring mandibular alveolar bone mineral density (BMD) was applied to 40 postmenopausal Japanese women aged 50-69 years exhibiting minimal to mild periodontal diseases. Lumbar spine BMD was measured by dual X-ray absorptiometry (DXA) and calcaneus speed of sound (SOS) by quantitative ultrasound (QUS). There were age-related decreases of alveolar BMD, calcaneus SOS and vertebral BMD. There were significant correlations between two of the respective bone mass values. Correlations between clinical dental findings and bone mass data including alveolar BMD, SOS and lumbar spine BMD were investigated. Significant correlations were demonstrated between alveolar BMD and calcaneus SOS or vertebral BMD. Alveolar BMD showed significant correlation with clinical dental findings including periodontal pocket depth and mobility as well as calcaneus SOS and lumbar spine BMD. Using multivariate analysis combinations of univariate predictors, including deoxypyridinoline (DPD), significantly predicted attachment levels. The SOS value was useful combined with other predictors for predicting attachment level. It was concluded that the new method of evaluating alveolar BMD is useful to predict systemic bone mass and strength as well as dental clinical findings.

Natural killer (NK) cells play a key role in inflammation and tumor regression through their ability to migrate into tissues. CXCL12 is a chemokine that promotes lymphocyte invasion and migration into tissues; however, the mechanism for this process remains incompletely understood. In this study, we show that CXCL12 significantly enhanced CD16 ؉ CD56 ؉ human peripheral NK-cell invasion into type I collagen by the catalytic activity of matrix metalloproteinase-1 (MMP-1). Confocal immunofluorescence and co-immunoprecipitation studies suggest that MMP-1 colocalized with ␣ 2 ␤ 1 integrin on CXCL-12-stimulated NK-cell surface. The binding of pro-MMP-1 with ␣ 2 ␤ 1 integrin required activation of G icoupled pathway. However, the production of MMP-1 from CXCL12-stimulated NK cells was mediated by p38 and mitogen-activated or extracellular signal-regulation protein kinase kinase 1/2 in a manner independent of the G i -coupled pathway. These results suggest that CXCL12/CXCR4 interaction transduces the two signaling pathways to promote NK-cell invasion, which stimulates pericellular degradation of extracellular matrix proteins by membrane-associated MMP-1. The mechanisms would thus play a role in facilitating lymphocyte trafficking and accumulation in tissues during physiological and pathological processes.

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SummaryAlveolar bone mineral density (BMD) measured by radiography standardized by aluminum step wedge pasted on the film and digitized by a computer system was significantly higher around osteonecrosis lesions than in control cases in a pilot case–control study. High alveolar bone density appears useful as a local risk factor for bisphosphonate-related osteonecrosis of the jaw (BRONJ).IntroductionIn an attempt to find a reliable test method predicting the occurrence of BRONJ in addition to various risk factors suggested, an increase of alveolar bone density near the necrotic lesions was found by computerized radiogrammetry using dental films pasted with an aluminum step wedge (Bone RightⓇ, Dentalgraphic⋅Com Company, Himeji) in six cases of BRONJ.MethodsThe bone mineral density surrounding the osteonecrosis lesions showed distinctly higher density in BRONJ cases compared with age-matched controls. In one subject on bisphosphonate treatment in whom two extractions were simultaneously carried out, BRONJ occurred only at the location with extremely high alveolar bone density, but not at the other site with normal density.ConclusionThis method may be useful in detecting a rise of alveolar BMD frequently occurring near the necrotic lesion in subjects with impending risk for BRONJ.

Vγ9Vδ2 T cells, the major subset of the human peripheral blood γδ T-cell, respond to microbial infection and stressed cells through the recognition of phosphoantigens. In contrast to the growing knowledge of antigen-mediated activation mechanisms, the antigen-independent and cytokine-mediated activation mechanisms of Vγ9Vδ2 T cells are poorly understood. Here, we show that interleukin (IL) -12 and IL-18 synergize to activate human ex vivo-expanded Vγ9Vδ2 T cells. Vγ9Vδ2 T cells treated with IL-12 and IL-18 enhanced effector functions, including the expression of IFN-γ and granzyme B, and cytotoxicity. These enhanced effector responses following IL-12 and IL-18 treatment were associated with homotypic aggregation, enhanced expression of ICAM-1 and decreased expression of the B- and T-lymphocyte attenuator (BTLA), a co-inhibitory receptor. IL-12 and IL-18 also induced the antigen-independent proliferation of Vγ9Vδ2 T cells. Increased expression of IκBζ, IL-12Rβ2 and IL-18Rα following IL-12 and IL-18 stimulation resulted in sustained activation of STAT4 and NF-κB. The enhanced production of IFN-γ and cytotoxic activity are critical for cancer immunotherapy using Vγ9Vδ2 T cells. Thus, the combined treatment of ex vivo-expanded Vγ9Vδ2 T cells with IL-12 and IL-18 may serve as a new strategy for the therapeutic activation of these cells.