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We studied MMP-8 in<jats:italic>Porphyromonas gingivalis<\/jats:italic>-induced periodontitis by using MMP-8-deficient (<jats:italic>MMP8<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>) and wild-type (WT) mice. Alveolar bone loss, inflammatory mediator expression, serum immunoglobulin, and lipoprotein responses were investigated to clarify the role of MMP-8 in periodontitis and systemic inflammatory responses.<jats:italic>P. gingivalis<\/jats:italic>infection induced accelerated site-specific alveolar bone loss in both<jats:italic>MMP8<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>and WT mice relative to uninfected mice. The most extensive bone degradation took place in the<jats:italic>P. gingivalis<\/jats:italic>-infected<jats:italic>MMP8<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>group. Surprisingly, MMP-8 significantly attenuated (<jats:italic>P<\/jats:italic>&lt; 0.05)<jats:italic>P. gingivalis<\/jats:italic>-induced site-specific alveolar bone loss. Increased alveolar bone loss in<jats:italic>P. gingivalis<\/jats:italic>-infected<jats:italic>MMP8<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>and WT mice was associated with increase in gingival neutrophil elastase production. Serum lipoprotein analysis demonstrated changes in the distribution of high-density lipoprotein (HDL) and very-low-density lipoprotein (VLDL) particles; unlike the WT mice, the<jats:italic>MMP8<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice underwent a shift toward a smaller HDL\/VLDL particle sizes.<jats:italic>P. gingivalis<\/jats:italic>infection increased the HDL\/VLDL particle size in the<jats:italic>MMP<\/jats:italic>8<jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice, which is an indicator of lipoprotein responses during systemic inflammation. Serum total lipopolysaccharide activity and the immunoglobulin G-class antibody level in response to<jats:italic>P. gingivalis<\/jats:italic>were significantly elevated in both infected mice groups. Thus, MMP-8 appears to act in a protective manner inhibiting the development of bacterium-induced periodontal tissue destruction, possibly through the processing anti-inflammatory cytokines and chemokines. Bacterium-induced periodontitis, especially in<jats:italic>MMP8<\/jats:italic><jats:sup><jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice, is associated with systemic inflammatory and lipoprotein changes that are likely involved in early atherosclerosis.<\/jats:p>","DOI":"10.1128\/iai.00873-08","type":"journal-article","created":{"date-parts":[[2008,11,25]],"date-time":"2008-11-25T01:50:29Z","timestamp":1227577829000},"page":"850-859","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":141,"title":["Local and Systemic Responses in Matrix Metalloproteinase 8-Deficient Mice during<i>Porphyromonas gingivalis<\/i>-Induced Periodontitis"],"prefix":"10.1128","volume":"77","author":[{"given":"Heidi","family":"Kuula","sequence":"first","affiliation":[{"name":"Institute of Dentistry, University of Helsinki, Biomedicum, P.O. Box 63, FIN-00014, Helsinki, Finland, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuula","family":"Salo","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, University of Oulu, P.O. Box 5281, 90014 University of Oulu, Oulu, Finland, and Oulu University Central Hospital, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Pirila\u0308","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, University of Oulu, P.O. Box 5281, 90014 University of Oulu, Oulu, Finland, and Oulu University Central Hospital, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita M.","family":"Tuomainen","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, University of Helsinki, Biomedicum, P.O. Box 63, FIN-00014, Helsinki, Finland, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matti","family":"Jauhiainen","sequence":"additional","affiliation":[{"name":"National Public Health Institute and FIMM, Institute for Molecular Medicine, Biomedicum, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli-Jukka","family":"Uitto","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, University of Helsinki, Biomedicum, P.O. Box 63, FIN-00014, Helsinki, Finland, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leo","family":"Tja\u0308derhane","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, University of Helsinki, Biomedicum, P.O. Box 63, FIN-00014, Helsinki, Finland, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland"},{"name":"Institute of Dentistry, University of Oulu, P.O. Box 5281, 90014 University of Oulu, Oulu, Finland, and Oulu University Central Hospital, Oulu, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pirkko J.","family":"Pussinen","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, University of Helsinki, Biomedicum, P.O. Box 63, FIN-00014, Helsinki, Finland, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Sorsa","sequence":"additional","affiliation":[{"name":"Institute of Dentistry, University of Helsinki, Biomedicum, P.O. 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