Abstract
Periodontal diseases are chronic inflammation caused by particular types of bacteria and have been recognized as a cause of tooth loss in adults. These bacteria which invade periodontal tissue are phagocytosed mainly by monocytes and macrophages in this immune response, and will be presented to lymphocytes. Recently, therapies for regenerating periodontal tissues have been used extensively to treat periodontal disease, and in particular, enamel matrix derivative (EMD) is commonly used for such therapies in Japan. Amelogenin is a type of the extracellular matrix protein that accounts for 90% of the constituents of EMD. In this study, we carried out a detailed microarray analysis in order to evaluate a gene group involved in amelogenin stimuli in the human monocytic cell line U-937. Microarray analysis revealed that statistically significant changes were apparent in 273 genes (163 up-regulated and 110 down-regulated) subsequent to 4 h of amelogenin stimulation. The most highly enriched categories included “cell cycle”, “DNA replication”, and “DNA repair” in up-regulated annotation terms. On the other hand, “type I diabetes mellitus”, “allograft rejection”, and “graft versus host disease” were observed in down-regulated annotation terms. Specifically, the gene expression of major to compatibility complex (MHC) class I/II and CD80/86 was impaired in U937 cells after stimulation with amelogenin. In addition, the results of heat-map showed that the gene expression of inflammatory cytokine such as tumor necrosis factor (TFN), interleukin-18 (IL-18), and CXCL16 was markedly decreased after stimulation of monocytes with amelogenin. In conclusion, the findings of our study showed that by inducing monocyte growth through the suppression of the antigen-presenting ability of U937 cells, amelogenin may affect the immune responses of periodontal tissues originating from monocytes. Examining the effects of amelogenin on the transformation of macrophages differentiating from monocytes may establish a molecular basis for the anti-inflammatory effect of amelogenin in periodontal tissues.
Highlights
Periodontal diseases are chronic inflammation caused by particular types of periodontal disease-causing bacteria
Periodontal diseases are chronic inflammation caused by particular types of bacteria and have been recognized as a cause of tooth loss in adults
By proteomic analysis focusing on amelogenin, which is a major protein in enamel matrix derivative (EMD), we identified a new group of amelogenin-associated molecules such as Grp78 in osteoblasts [14]
Summary
Periodontal diseases are chronic inflammation caused by particular types of periodontal disease-causing bacteria. Because they cause resorption of the alveolar bone, they have been recognized as a cause of tooth loss in adults aged 40 years or older [1]. Recently developed regenerative therapies aimed at regenerating periodontal tissues have been used extensively to treat periodontal disease, and some success has been achieved [4]. Among periodontal tissue regeneration materials that contain bioactive proteins such as growth factors, Emdogain® gel is currently the only treatment approved by the Japanese Ministry of Health, Labour and Welfare. Periodontal surgical treatment using EMD has been empirically shown to promote healing and is associated with reduced pain and swelling [6]. Previous reports have shown that amelogenin had an anti-inflammatory effect from the perspective of pro-inflammatory and anti-inflammatory cytokine production [7]
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