Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts.
Gram-positive bacteria cell wall-derived lipoteichoic acid induces inflammatory alveolar bone loss through prostaglandin E production in osteoblasts.
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DOI：
10.1038/s41598-021-92744-5
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发表时间：
2021-06-25
影响因子：
4.6
通讯作者：
Inada M
中科院分区：
文献类型：
--
作者：
Tominari T;Sanada A;Ichimaru R;Matsumoto C;Hirata M;Itoh Y;Numabe Y;Miyaura C;Inada M
牙周炎是一种与严重牙槽骨丢失相关的炎性疾病，主要由革兰氏阴性菌的脂多糖引起;然而，革兰氏阳性菌在牙周骨吸收中的作用尚不清楚。在这项研究中，我们研究了脂磷壁酸（LTA），革兰氏阳性菌的主要细胞壁因子，牙周炎模型中炎症性牙槽骨丢失的进展的影响。在小鼠原代成骨细胞和骨髓细胞共培养中，LTA以剂量依赖的方式诱导破骨细胞分化。LTA可促进成骨细胞PGE 2的生成，并上调mPGES-1、考克斯-2和RANKL的mRNA表达。吲哚美辛的加入通过抑制PGE 2的产生有效地阻断了LTA诱导的破骨细胞分化。使用离体小鼠牙槽骨器官培养，我们发现，LTA诱导牙槽骨吸收，这是抑制消炎痛。在实验性牙周炎模型中，将LTA局部注射到小鼠下牙龈中，我们使用3D-μCT清楚地检测到牙槽骨破坏。我们在此提出了一个新的概念，即除了革兰氏阴性菌外，革兰氏阳性菌也与牙周骨丢失的进展有关。
Periodontitis is an inflammatory disease associated with severe alveolar bone loss and is dominantly induced by lipopolysaccharide from Gram-negative bacteria; however, the role of Gram-positive bacteria in periodontal bone resorption remains unclear. In this study, we examined the effects of lipoteichoic acid (LTA), a major cell-wall factor of Gram-positive bacteria, on the progression of inflammatory alveolar bone loss in a model of periodontitis. In coculture of mouse primary osteoblasts and bone marrow cells, LTA induced osteoclast differentiation in a dose-dependent manner. LTA enhanced the production of PGE2 accompanying the upregulation of the mRNA expression of mPGES-1, COX-2 and RANKL in osteoblasts. The addition of indomethacin effectively blocked the LTA-induced osteoclast differentiation by suppressing the production of PGE2. Using ex vivo organ cultures of mouse alveolar bone, we found that LTA induced alveolar bone resorption and that this was suppressed by indomethacin. In an experimental model of periodontitis, LTA was locally injected into the mouse lower gingiva, and we clearly detected alveolar bone destruction using 3D-μCT. We herein demonstrate a new concept indicating that Gram-positive bacteria in addition to Gram-negative bacteria are associated with the progression of periodontal bone loss.
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