PKR regulates LPS-induced osteoclast formation and bone destruction in vitro and in vivo.
PKR regulates LPS-induced osteoclast formation and bone destruction in vitro and in vivo.
复制标题
PKR 在体外和体内调节 LPS 诱导的破骨细胞形成和骨破坏。
DOI：
10.1111/odi.12592
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
Haneji T.
中科院分区：
文献类型：
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作者：
Teramachi J;Inagaki Y;Shinohara H;Okamura H;Yang D;Ochiai K;Baba R;Morimoto H;Nagata T;Haneji T.
在这项研究中，我们旨在阐明脂多糖（LPS）诱导的破骨细胞在牙周病中的确切机制，特别是双链RNA依赖的蛋白激酶（PKR）。材料和方法我们解剖了PKR在LPS诱导的破骨细胞分化和功能中的作用，使用原代小鼠骨髓细胞和RAW 264. 7前骨细胞系。我们使用大鼠实验性牙周炎（PD）模型与牙龈卟啉单胞菌脂多糖注射（PD大鼠）结扎放置诱导和分析的治疗效果C16，PKR抑制剂，在PD rats.ResultsProtein kinase强烈上调和磷酸化的破骨细胞中的骨丢失。PKR的抑制抑制了LPS刺激的破骨细胞的形成和活化。PKR抑制还抑制了LPS介导的NF-κB和MAPK活化，这是破骨细胞生成的关键途径。PKR在PD大鼠破骨细胞中高表达，C16治疗可有效防止PD大鼠牙槽骨破坏。结论PKR在LPS诱导的PD骨丢失中起关键作用，有望成为PD的治疗靶点。
ObjectiveIn this study, we aimed to clarify the precise mechanism underlying lipopolysaccharide (LPS)‐induced osteoclastogenesis in periodontal disease with a special reference to double‐stranded RNA‐dependent protein kinase (PKR).Material and MethodsWe dissected the role of PKR in LPS‐induced osteoclast differentiation and function using primary mouse bone marrow cells and RAW264.7 pre‐osteoclastic cell line. We used a rat experimental periodontitis (PD) model induced by ligature placement with a Porphyromonas gingivalis LPS injection (PD rat) and analyzed the therapeutic effects of C16, a PKR inhibitor, on bone loss in PD rats.ResultsProtein kinase is strongly upregulated and phosphorylated by LPS in the osteoclasts. The inhibition of PKR suppressed LPS‐stimulated osteoclast formation and activation. PKR inhibition also suppressed the LPS‐mediated activation of NF‐κB and MAPK, which are critical pathways for osteoclastogenesis. High expressions of PKR were detected in osteoclasts of PD rats, and the treatment with C16 effectively prevented alveolar bone destruction in PD rats.ConclusionsPKR plays a pivotal role in LPS‐induced bone loss in PD and, thus, has potential as a therapeutic target for PD.