Zhao Panyu, Liu Junchao, Pan Chunling, Pan Yaping
Department of Pediatric Dentistry, School of Stomatology, China Medical University, Shenyang 110001, People's Republic of China.
Department of Oral Biology and Periodontics, School of Stomatology, China Medical University, Shenyang 110001, People's Republic of China.
Acta Histochem. 2014 Sep;116(7):1119-24. doi: 10.1016/j.acthis.2014.05.008. Epub 2014 Jul 4.
Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is a Gram-negative bacterium which is implicated in the pathogenesis of human periodontal disease and in particular aggressive periodontitis. Virulence factors from A. actinomycetemcomitans have been shown to induce apoptosis of osteoblasts, however, the underlying mechanisms of the induction of apoptosis are poorly understood. In the present study, the infection of A. actinomycetemcomitans in human osteoblastic MG63 cells was established. Accordingly, A. actinomycetemcomitans infection enhanced significant apoptosis of MG63 cells. We found that both expression levels of NLRP3 and ASC were increased dramatically after MG63 cell cultures exposed to A. actinomycetemcomitans. Moreover, the secretion of mature interleukin-1β (IL-1β) and IL-18 were extensively induced in A. actinomycetemcomitans-infected cells as compared with non-invasion group of MG63 cell cultures, indicating the activation of the NLRP3 inflammasome during infection. Finally, we found that the knockdown expression of NLRP3 by specific small interfering RNA (siRNA) attenuated apoptosis of A. actinomycetemcomitans-infected MG63 cells. Our data suggest that A. actinomycetemcomitans promotes apoptosis of human osteoblasts at least partially through the NLRP3 inflammasome.
伴放线聚集杆菌（A. actinomycetemcomitans）是一种革兰氏阴性菌，与人类牙周疾病尤其是侵袭性牙周炎的发病机制有关。已证明伴放线聚集杆菌的毒力因子可诱导成骨细胞凋亡，然而，其诱导凋亡的潜在机制尚不清楚。在本研究中，建立了伴放线聚集杆菌感染人成骨MG63细胞的模型。相应地，伴放线聚集杆菌感染显著增强了MG63细胞的凋亡。我们发现，MG63细胞培养物暴露于伴放线聚集杆菌后，NLRP3和ASC的表达水平均显著增加。此外，与未侵袭的MG63细胞培养组相比，伴放线聚集杆菌感染的细胞中成熟白细胞介素-1β（IL-1β）和IL-18的分泌大量增加，表明感染期间NLRP3炎性小体被激活。最后，我们发现通过特异性小干扰RNA（siRNA）敲低NLRP3的表达可减轻伴放线聚集杆菌感染的MG63细胞的凋亡。我们的数据表明，伴放线聚集杆菌至少部分通过NLRP3炎性小体促进人成骨细胞凋亡。
