Frontline Science: Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection
| Autor: | Yanfang Zhao, Ping Zhang, Lingkai Su, Zhaofei Li, Jannet Katz, Xu Feng, André Ballesteros-Tato, Suzanne M. Michalek |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Myeloid Immunology Population Osteoclasts Biology Mice 03 medical and health sciences 0302 clinical medicine Osteoclast Immunity Bacteroidaceae Infections medicine Animals Immunology and Allergy RNA-Seq Bone Resorption education Porphyromonas gingivalis Mice Knockout education.field_of_study Stem Cells Cell Biology biology.organism_classification Disease Models Animal Chronic infection 030104 developmental biology medicine.anatomical_structure MRNA Sequencing 030220 oncology & carcinogenesis Chronic Disease Bone marrow |
| Zdroj: | Journal of Leukocyte Biology. 108:1037-1050 |
| ISSN: | 1938-3673 0741-5400 |
| DOI: | 10.1002/jlb.1hi0620-230r |
| Popis: | 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+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 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text