Inhibition of tissue-reparing signaling by P.gingivalis infection

牙龈卟啉单胞菌感染对组织修复信号的抑制

• 批准号: 15390645
• 负责人: OKAHASHI Nobuo
• 金额: $ 5.06万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390645/
• 关键词: periodontitis; tissue regeneration; P.gingivalis; cellular attachment; epithelial cells; periodontal ligament cells; 骨芽細胞

P.gingivalis, a periodontopathic Gram-negative bacteria, is known to invade into a variety of host cells such as epithelial cells and fibroblasts. A chronic inflammation of infected periodontal tissue results in tissue destruction. In this study, we investigated the involvement of the two major virulent factors of this pathogen ; fimbriae and a protease called gingipain on the destruction and inhibition of regeneration of infected host tissues.At first, we constructed fimbriae-deficient and gingipain-deficient mutants of P.gingivalis. Using these two mutants, we found that :1)Both fimbriae- and gingipain-deficient mutants of P.gingivalis showed decreased invasion in human periodontal ligament cells (PDLs).2)Infection of wild type of P.gingivalis in serum-free medium resulted in a detachment of PDLs from the culture dishes. However, gingipain-deficient mutant did not induce such detachment of PDLs.3)Infection of wild type of P.gingivalis induced a degradation of integrin-associated signaling molecules such as FAK and paxillin. However, the degradation of FAK and paxillin was not observed during infection with gingipain-deficient mutant.4)By using a scratch assay, we found that the infection of P.gingivalis strongly inhibited the regeneration of damaged monolayers of PDLs. The bacterial infection inhibited the cellular movement as well as the cellular growth.5)Gingipain-deficient mutant did not show the inhibitory effect on the regeneration of the infected cellular monolayers. On the other hand, fimbriae-deficient mutant did inhibit the regeneration process.These results strongly suggested that gingipain of P.gingivalis plays an important role in the inhibition of regeneration of the infected periodontal tissues.

牙龈卟啉单胞菌（P.gingivalis）是一种引起牙周病的革兰氏阴性细菌，已知其可侵入多种宿主细胞，如上皮细胞和成纤维细胞。受感染牙周组织的慢性炎症导致组织破坏。在这项研究中，我们调查了这种病原体的两个主要的毒力因子的参与;菌毛和蛋白酶称为gingipain的破坏和抑制感染的宿主tissues.At再生首先，我们构建了菌毛缺陷和gingipain缺陷的牙龈卟啉单胞菌的突变体。结果发现：1）牙龈卟啉单胞菌菌毛和牙龈卟啉蛋白酶缺陷型均能降低牙龈卟啉单胞菌对人牙周膜细胞的侵袭能力; 2）无血清培养条件下，野生型牙龈卟啉单胞菌感染后，牙周膜细胞脱离培养皿。然而，牙龈卟啉菌蛋白酶缺陷型突变体不诱导PDL的这种脱离。3）感染野生型牙龈卟啉菌诱导整合素相关信号分子如FAK和桩蛋白的降解。然而，在牙龈卟啉单胞菌蛋白酶缺陷型MUSCLE感染过程中没有观察到FAK和桩蛋白的降解。4）通过划痕试验，我们发现牙龈卟啉单胞菌感染强烈抑制了受损的PDL单层的再生。5）Gingipain缺陷突变体对感染细胞单层的再生无抑制作用。而菌毛缺失的突变体则抑制了牙周组织的再生，这一结果表明牙龈卟啉菌的牙龈蛋白酶在抑制牙周组织再生中起重要作用。

项目成果

Comparison of inflammatory changes caused by Porphyromonas gingivalis with distinct fimA genotypes in a mouse abscess model

• DOI: 10.1111/j.0902-0055.2004.00133.x
• 发表时间: 2004-06-01
• 期刊: ORAL MICROBIOLOGY AND IMMUNOLOGY
• 作者: Nakano, K;Kuboniwa, M;Amano, A
• 通讯作者: Amano, A

Nakagawa I, Kurokawa K, Yamashita A, Nakata M, Tomiyasu Y, Okahashi N, Kawabata S, Yamazaki K, Shiba T, Yasunaga T, Hayashi H, Hattori M, Hamada S.: "Genomic sequence of an M3 strain of Streptococcus pyogenes reveals a large scale genomic rearrangement in

Nakakawa I、Kurokawa K、Yamashita A、Nakata M、Tomiyasu Y、Okahashi N、Kawabata S、Yamazaki K、Shiba T、Yasunaga T、Hayashi H、Hattori M、Hamada S.：“化脓性链球菌 M3 菌株的基因组序列

Porphyromonas gingivalis induces receptor activator of NF-kB ligand expression in osteoblasts throuhg the activator protein-1 pathway.

牙龈卟啉单胞菌通过激活蛋白 1 途径诱导成骨细胞中 NF-kB 受体激活剂配体的表达。

• 发表时间: 2004
• 期刊: Infection and Immunity 72
• 作者: Okahashi;N.;Inaba;H.;Nakagawa;I.;Yamamura;T.;Kuboniwa;M.;Nakayama;K.;Hamada;S.;Amano;A.
• 通讯作者: A.

Okahashi N, Sakurai A, Nakagawa I, Fujiwara T, Kawabata S, Amano A, Hamada S.: "Infection by Streptococcus pyogenes induces the receptor activator of NF-kB ligand expression in mouse osteoblastic cells"Infection and Immunity. 71. 948-955 (2003)

Okahashi N、Sakurai A、Nakakawa I、Fujiwara T、Kawabata S、Amano A、Hamada S.：“化脓性链球菌感染诱导小鼠成骨细胞中 NF-kB 配体表达的受体激活剂”感染和免疫。

Itoh K, Udagawa N, Kobayashi K, Suda K, Li X, Takami M, Okahashi N, Nishihara T, Takahashi N.: "Lipopolysaccharide promotes the survival of osteoclasts via Toll-like receptor 4, but cytokine production of osteoclasts in response to lipopolysaccharide is d

Itoh K、Udakawa N、Kobayashi K、Suda K、Li X、Takami M、Okahashi N、Nishihara T、Takahashi N.：“脂多糖通过 Toll 样受体 4 促进破骨细胞的存活，但破骨细胞的细胞因子产生响应于