Frontline Science: Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection,Journal of Leukocyte Biology

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Frontline Science: Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection
Journal of Leukocyte Biology ( IF 3.6 ) Pub Date : 2020-08-17 , DOI: 10.1002/jlb.1hi0620-230r
Yanfang Zhao ₁ , Zhaofei Li ₁ , Lingkai Su ₁ , Andre Ballesteros-Tato ₂ , Jannet Katz ₁ , Suzanne M Michalek ₃ , Xu Feng ₄ , Ping Zhang ₁

Affiliation

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 microosmotic pump to continually release Pg subcutaneously in a murine model. Two weeks after Pg infection, the frequency of CD11b⁺c‐fms⁺Ly6C^hi 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⁺Ly6C^hi 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⁺Ly6C^hi population from the bone marrow and periphery. Our results provide new insight 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.

中文翻译：

前沿科学：慢性牙龈卟啉单胞菌感染后破骨细胞前体的表征和调控

包括牙周炎在内的炎性溶骨性疾病中的骨破坏与破骨细胞 (OC) 的过度活动有关，破骨细胞起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 的丰富知识相比，我们对 OCP 及其在细菌感染过程中的调节知之甚少。因此，本研究旨在鉴定和表征牙周细菌牙龈卟啉单胞菌( Pg )慢性感染后的 OCP 。我们使用微渗泵在小鼠模型中持续皮下释放Pg。Pg感染两周后，CD11b ⁺ c-fms ⁺ Ly6C ^hi的频率骨髓、脾脏和外周血中的人口显着升高。体外和体内研究将这些细胞鉴定为含有 OCP 的群体，Pg感染显着增强了这些细胞的破骨细胞活性。此外，mRNA 测序分析表明Pg感染后 CD11b ⁺ c-fms ⁺ Ly6C ^hi群体中存在独特的基因和通路谱，与 OC 分化、细胞增殖和凋亡、炎症反应、吞噬作用和免疫相关的基因和通路发生变化，以及抗原加工和呈递。此外，使用 IL-6 敲除小鼠，我们发现 IL-6 对Pg很重要从骨髓和外周诱导 CD11b ⁺ c-fms ⁺ Ly6C ^hi群体的积累。我们的研究结果为慢性细菌感染后 OCP 的表征和调节提供了新的见解。这些知识与了解细菌引起的骨质流失的发病机制以及确定骨质流失疾病的潜在治疗靶点有关。

更新日期：2020-09-30

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