Premium
Frontline Science: Characterization and regulation of osteoclast precursors following chronic Porphyromonas gingivalis infection
Author(s) -
Zhao Yanfang,
Li Zhaofei,
Su Lingkai,
BallesterosTato Andre,
Katz Jannet,
Michalek Suzanne M,
Feng Xu,
Zhang Ping
Publication year - 2020
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.1hi0620-230r
Subject(s) - porphyromonas gingivalis , osteoclast , biology , bone marrow , immunology , population , periodontitis , immune system , integrin alpha m , in vivo , spleen , phagocytosis , myeloid , microbiology and biotechnology , in vitro , medicine , genetics , environmental health
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.