This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Osteoclasts are multinucleated and highly motile cells responsible for bone resorption. Matrix metalloproteinases (MMPs) have been reported to be critical for promoting osteoclast migration to bone resorption sites. To date, there is still a knowledge gap regarding whether and how periodontal pathogens have direct effect on migration ability in various stages of differentiating cells of osteoclastogenesis. The overall objective of this study is to determine the role and mechanisms of Porphyromonas gingivalis (P. gingivalis), a major periodontal pathogen, in regulating collagen degradation and MMP-9 and MMP-14 expression in two differentiation stages of osteoclasts: monocytes and pre-osteoclasts. The central hypothesis is that P. gingivalis can enhance collagen degrading ability by stimulating MMP expression and activation in human monocytes and pre-osteoclasts, thus promoting the migratory ability of osteoclastogenetic cells. There are three specific aims: 1. To determine whether culture supernatant of P. gingivalis augments collagen degradation ability in human pre-osteoclasts. 2. To determine the effect of culture supernatant of P. gingivalis on MMP-9 and MMP-14 activation and expression in monocytes and pre-osteoclasts. 3. To determine the role of MMPs in pre-osteoclast and monocyte migration induced by P. gingivalis. These pilot studies will provide important information for further investigating the role of MMPs in osteoclast migration, differentiation, and function. In the long term, this study will provide significant insights into the mechanisms by which periodontal pathogens promote osteoclast migration, and will aid in the identification of novel targeting molecules for bone degrading processes during periodontal diseases.
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