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The core PAMP and DAMP prototype molecules are periodontal bacterium\n                    <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    \u2013derived virulence lipids, for example,\n                    <jats:italic>phosphoglycerol<\/jats:italic>\n                    dihydroceramide (PGDHC) and lipopolysaccharide (LPS\n                    <jats:italic>Pg<\/jats:italic>\n                    ), and the host non\u2010histone alarmin high mobility group box protein\u20101 (HMGB1), respectively. Although it was reported that extracellularly released HMGB1 is critical for the promotion of sepsis inflammation in response to non\u2010periodontal bacterial LPS, our understanding of the crosstalk between HMGB1 and\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    \u2013derived virulence lipids remains limited. Therefore, we used Hmgb1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    LysM\u2010Cre\n                    <jats:sup>+<\/jats:sup>\n                    mice with ablated HMGB1 mRNA and littermate Hmgb1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    LysM\u2010Cre\n                    <jats:sup>\u2212<\/jats:sup>\n                    controls. We observed limited Hmgb1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    LysM\u2010Cre\n                    <jats:sup>+<\/jats:sup>\n                    osteoclastogenesis compared to Hmgb1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    in response to RANKL in vitro. Furthermore, recombinant HMGB1 protein restored osteoclast formation in Hmgb1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    LysM\u2010Cre\n                    <jats:sup>+<\/jats:sup>\n                    cells, indicating the pivotal role of extracellular HMGB1 in osteoclastogenesis in vitro. Using bulk RNA\u2010sequencing, we identified the diminished osteoclastogenesis in Hmgb1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    LysM\u2010Cre\n                    <jats:sup>+<\/jats:sup>\n                    cells are linked to accelerated expression of canonical osteoclast\u2010suppressing interferon genes. We surprisingly detected that PGDHC and LPS\n                    <jats:italic>Pg<\/jats:italic>\n                    accelerate osteoclastogenesis in Hmgb1\n                    <jats:sup>fl\/fl<\/jats:sup>\n                    LysM\u2010Cre\n                    <jats:sup>+<\/jats:sup>\n                    cells in vitro. Using bulk RNA\u2010sequencing and real\u2010time PCR assays, we confirmed that PGDHC diminishes the expression patterns of different interferon\u2010inducible guanylate\u2010binding proteins (\n                    <jats:italic>GBP 3<\/jats:italic>\n                    ,\n                    <jats:italic>4<\/jats:italic>\n                    ,\n                    <jats:italic>5<\/jats:italic>\n                    ,\n                    <jats:italic>9<\/jats:italic>\n                    ). At the same time, LPS Pg accelerates the expression of osteoclast\u2010promoting matrix metalloproteases (\n                    <jats:italic>MMP 8<\/jats:italic>\n                    and\n                    <jats:italic>12<\/jats:italic>\n                    ) mRNAs. The results suggest that the RANKL\u2010primed osteoclastogenesis accelerated by\n                    <jats:italic>P. gingivalis<\/jats:italic>\n                    \u2013derived virulence lipids is mediated by different MMP or GBP signaling pathways independently from canonical HMGB1 signaling.\n                  <\/jats:p>","DOI":"10.1111\/omi.70015","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T06:05:56Z","timestamp":1765173956000},"page":"85-93","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["<i>Porphyromonas gingivalis<\/i>\n                    \u2013Derived Virulence Lipids Accelerate Osteoclastogenesis Independently of High Mobility Group Box Protein\u20101 Canonical Signaling"],"prefix":"10.1111","volume":"41","author":[{"given":"Chiaki","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Biomedical and Applied Sciences Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Richard L. Roudebush VA Medical Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Peng","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"James A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amilia","family":"Nusbaum","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Applied Sciences Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Sanz","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Applied Sciences Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hawra","family":"AlQallaf","sequence":"additional","affiliation":[{"name":"Department of Periodontology Indiana University School of Dentistry  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6800-1112","authenticated-orcid":false,"given":"Frank","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Periodontology University of Connecticut School of Dental Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-7347","authenticated-orcid":false,"given":"Alexandru","family":"Movila","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Applied Sciences Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Richard L. 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