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However, beyond the knowledge that osteoclasts are differentiated from the monocyte\/macrophage lineage and share common ancestry with macrophages and DC, the nature and function of osteoclast precursors are not completely understood. Furthermore, little is known about how osteoclast precursors respond to bacterial infection in vivo. We have previously demonstrated in vitro that the periodontal pathogen <jats:italic>Porphyromonas gingivalis<\/jats:italic> (<jats:italic>Pg<\/jats:italic>) plays a biphasic role on the receptor activator of nuclear factor kappa B ligand (RANKL)\u2013induced osteoclast differentiation. In this study, we investigated the in vivo effect of <jats:italic>Pg<\/jats:italic> infection on the regulation of osteoclast precursors, using a mouse calvarial infection model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>C57BL\/6 wild\u2010type and the myeloid differentiation factor 88 knockout (MyD88<jats:sup>\u2212\/\u2212<\/jats:sup>) mice were infected with <jats:italic>Pg<\/jats:italic> by calvarial injection. Local and systemic bone loss, and the number and function of CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup> cells from bone marrow and spleen were analyzed. Our results show that <jats:italic>Pg<\/jats:italic> infection induces localized inflammatory infiltration and osteoclastogenesis, as well as increased number and osteoclastogenic potential of CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup> osteoclast precursors in the bone marrow and periphery. We also show that CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup>RANK<jats:sup>+<\/jats:sup> and CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup>RANK<jats:sup>\u2212<\/jats:sup> are precursors with similar osteoclastogenic and pro\u2010inflammatory potentials. In addition, CD11b<jats:sup>+<\/jats:sup>c\u2010fms<jats:sup>+<\/jats:sup> cells exhibit an antigen\u2010specific T\u2010cell immune\u2010suppressive activity, which are increased with <jats:italic>Pg<\/jats:italic> infection. Moreover, we demonstrate that MyD88 is involved in the regulation of osteoclast precursors upon <jats:italic>Pg<\/jats:italic> infection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In this study, we demonstrate an enhanced dual function of osteoclast precursors following calvarial <jats:italic>Pg<\/jats:italic> infection. Based on our findings, we propose the following model: <jats:italic>Pg<\/jats:italic> infection increases a pool of precursor cells that can be shunted toward osteoclast formation at the infection\/inflammation sites, while at the same time dampening host immune responses, which is beneficial for the persistence of infection and maintenance of the characteristic chronic nature of periodontitis. Understanding the nature, function, and regulation of osteoclast precursors will be helpful for identifying therapeutic interventions to aid in the control and prevention of inflammatory bone loss diseases including periodontitis.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jre.12725","type":"journal-article","created":{"date-parts":[[2020,1,16]],"date-time":"2020-01-16T08:25:22Z","timestamp":1579163122000},"page":"410-425","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Enhanced dual function of osteoclast precursors following calvarial <i>Porphyromonas gingivalis<\/i> infection"],"prefix":"10.1111","volume":"55","author":[{"given":"Xia","family":"Cai","sequence":"first","affiliation":[{"name":"Department of Pediatric Dentistry School of Dentistry University of Alabama at Birmingham Birmingham AL USA"},{"name":"Department of Periodontics The Affiliated Stomatological Hospital School of Medicine Zhejiang University 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