ROLE OF MATRIX METALLOPROTEINASES IN PROPHYROMONOS GINGIVALIS-INDUCED OSTEOCLAST

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 破骨细胞是负责骨吸收的多核和高度能动性的细胞。据报道，基质金属蛋白酶(MMPs)在促进破骨细胞向骨吸收部位迁移方面起着关键作用。到目前为止，关于牙周病原体是否以及如何在破骨细胞分化的不同阶段对迁移能力产生直接影响仍存在知识空白。本研究旨在探讨牙周主要病原菌牙龈卟啉单胞菌(P.gigivalis)在破骨细胞两个分化阶段：单核细胞和破骨前细胞中对胶原降解和基质金属蛋白酶-9和基质金属蛋白酶-14表达的调节作用及其机制。中心假说是牙龈假单胞菌可以通过刺激人单核细胞和破骨前细胞中基质金属蛋白酶的表达和活化来增强胶原降解能力，从而促进破骨细胞的迁移能力。有三个具体目的：1.确定牙龈假单胞菌培养上清液是否能增强人破骨前细胞的胶原降解能力。2.检测牙龈假单胞菌培养上清对单核细胞和破骨前细胞中基质金属蛋白酶-9和基质金属蛋白酶-14的激活和表达的影响。3.探讨基质金属蛋白酶在牙龈假单胞菌诱导的破骨前细胞和单核细胞迁移中的作用。这些先导性研究将为进一步研究MMPs在破骨细胞迁移、分化和功能中的作用提供重要信息。从长远来看，这项研究将对牙周病原体促进破骨细胞迁移的机制提供重要的见解，并将有助于识别新的靶向分子，用于牙周疾病中的骨降解过程。

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.