Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection.
Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection.
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慢性牙龈卟啉单胞菌感染后破骨细胞前体细胞的特性分析与调控
DOI：
10.1002/jlb.1hi0620-230r
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发表时间：
2020-10
影响因子：
5.5
通讯作者：
Zhang P
中科院分区：
文献类型：
--
作者：
Zhao Y;Li Z;Su L;Ballesteros-Tato A;Katz J;Michalek SM;Feng X;Zhang P
炎症性溶骨性疾病（包括牙周炎）中的骨破坏与破骨细胞（OC）的过度活性有关，破骨细胞（OC）来源于髓系的前体细胞，称为破骨细胞前体（OCP）。与我们目前对成熟OC的充分了解相反，对OCP及其在细菌感染期间的调节知之甚少。因此，本研究的目的是确定和表征OCP慢性感染牙周细菌牙龈卟啉单胞菌（Pg）。我们使用微渗透泵在小鼠模型中持续皮下释放Pg。Pg感染后2周，CD 11b +c-fms+ Ly 6Chi群体在骨髓、脾脏和外周血中的频率显著升高。在体外和体内研究确定这些细胞作为OCP的人口和Pg感染显着增强破骨细胞的活性，这些细胞。此外，mRNA测序分析表明，在CD 11b +c-fms+ Ly 6Chi群体中，Pg感染后具有独特的基因和通路谱，与OC分化、细胞增殖和凋亡、炎症反应、吞噬和免疫以及抗原加工和呈递相关的基因和通路发生变化。此外，使用IL-6敲除小鼠，我们发现IL-6对于Pg诱导的CD 11b +c-fms+ Ly 6Chi群体从骨髓和外周的积累是重要的。我们的研究结果为慢性细菌感染后OCP的表征和调控提供了新的见解。这些知识对于理解细菌引起的骨丢失的发病机制以及确定骨丢失疾病的潜在治疗靶点是相关的。慢性牙龈卟啉单胞菌感染通过升高血清IL-6促进CD 11b +c-fms+ Ly 6 Chi OCP在BM和外周中的积累，并通过改变基因特征增强其破骨细胞生成潜力
Bone destruction in inflammatory osteolytic diseases including periodontitis is related to excessive activity of osteoclasts (OC), which originate from precursor cells of the myeloid lineage, termed osteoclast precursors (OCP). In contrast to ample knowledge that we currently have on mature OC, little is known about OCP and their regulation during bacterial infection. Therefore, this study aimed to identify and characterize OCP following chronic infection with a periodontal bacteria Porphyromonas gingivalis (Pg). We used a micro-osmotic pump to continually release Pg subcutaneously in a murine model. Two weeks after Pg infection, the frequency of CD11b+c-fms+Ly6Chi population is significantly elevated within the bone marrow, spleen and peripheral blood. In vitro and in vivo studies identified these cells as the OCP-containing population and Pg infection significantly enhanced the osteoclastogenic activity of these cells. Furthermore, mRNA sequencing analysis indicated a unique gene and pathway profile in CD11b+c-fms+Ly6Chi population following Pg infection, with changes in genes and pathways related to OC differentiation, cell proliferation and apoptosis, inflammatory response, phagocytosis and immunity, as well as antigen processing and presentation. Moreover, using IL-6 knockout mice, we found that IL-6 is important for Pg-induced accumulation of CD11b+c-fms+Ly6Chi population from the bone marrow and periphery. Our results provide new insights into the characterization and regulation of OCP following a chronic bacterial infection. This knowledge is relevant to the understanding of the pathogenesis of bacteria-induced bone loss, and to the identification of potential therapeutic targets of bone loss diseases. Chronic Porphyromonas gingivalis infection promotes CD11b+c-fms+Ly6Chi OCP accumulation in BM and periphery through elevated serum IL-6 and enhances their osteoclastogenic potential through changed gene signatures
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Keystone-Pathogen假设。
DOI：
10.1038/nrmicro2873
发表时间：
2012-10
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
通讯作者：
--
DOI：
10.1155/2011/765624
发表时间：
2011
期刊：
Arthritis
影响因子：
--
作者：
Hashizume M;Mihara M
通讯作者：
Mihara M
DOI：
10.1084/jem.190.12.1741
发表时间：
1999-12-20
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Arai F;Miyamoto T;Ohneda O;Inada T;Sudo T;Brasel K;Miyata T;Anderson DM;Suda T
通讯作者：
Suda T
影响因子：
4.9
作者：
Cremers NAJ;van den Bosch MHJ;van Dalen S;Di Ceglie I;Ascone G;van de Loo F;Koenders M;van der Kraan P;Sloetjes A;Vogl T;Roth J;Geven EJW;Blom AB;van Lent PLEM
通讯作者：
van Lent PLEM
影响因子：
3.1
作者：
Baker, PJ;Dixon, M;Roopenian, DC
通讯作者：
Roopenian, DC