title: Local and systemic responses in matrix metalloproteinase 8-deficient mice during Porphyromonas gingivalis-induced periodontitis.
abstract: Periodontitis is a bacterium-induced chronic inflammation that destroys tissues that attach teeth to jaw bone. Pathologically excessive matrix metalloproteinase 8 (MMP-8) is among the key players in periodontal destruction by initiating type I collagen degradation. We studied MMP-8 in Porphyromonas gingivalis-induced periodontitis by using MMP-8-deficient (MMP8(-/-)) 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. P. gingivalis infection induced accelerated site-specific alveolar bone loss in both MMP8(-/-) and WT mice relative to uninfected mice. The most extensive bone degradation took place in the P. gingivalis-infected MMP8(-/-) group. Surprisingly, MMP-8 significantly attenuated (P < 0.05) P. gingivalis-induced site-specific alveolar bone loss. Increased alveolar bone loss in P. gingivalis-infected MMP8(-/-) 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 MMP8(-/-) mice underwent a shift toward a smaller HDL/VLDL particle sizes. P. gingivalis infection increased the HDL/VLDL particle size in the MMP8(-/-) 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 P. gingivalis 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 MMP8(-/-) mice, is associated with systemic inflammatory and lipoprotein changes that are likely involved in early atherosclerosis.
authors.affiliation: Biomedicum Helsinki, Institute of Dentistry, P.O. Box 63 (Haartmaninkatu 8), 00014 University of Helsinki, Helsinki, Finland. heidi.kuula@helsinki.fi
authors.forename: Heidi
authors.initials: H
authors.lastname: Kuula
authors.forename: Tuula
authors.initials: T
authors.lastname: Salo
authors.forename: Emma
authors.initials: E
authors.lastname: Pirilä
authors.forename: Anita M
authors.initials: AM
authors.lastname: Tuomainen
authors.forename: Matti
authors.initials: M
authors.lastname: Jauhiainen
authors.forename: Veli-Jukka
authors.initials: VJ
authors.lastname: Uitto
authors.forename: Leo
authors.initials: L
authors.lastname: Tjäderhane
authors.forename: Pirkko J
authors.initials: PJ
authors.lastname: Pussinen
authors.forename: Timo
authors.initials: T
authors.lastname: Sorsa
mesh_terms: D016301:Alveolar Bone Loss / Q000382:microbiology / Q000473:pathology; D000818:Animals; D016866:Bacteroidaceae Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D020784:Matrix Metalloproteinase 8 / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010518:Periodontitis / Q000382:microbiology* / Q000473:pathology*; D016966:Porphyromonas gingivalis
chemical_list: D020784:Matrix Metalloproteinase 8