ROLE OF MATRIX METALLOPROTEINASES IN PROPHYROMONOS GINGIVALIS-INDUCED OSTEOCLAST

基质金属蛋白酶在牙龈前单胞菌诱导的破骨细胞中的作用

• 批准号: 8167772
• 负责人: Jing Zhou
• 金额: $ 3.55万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167772
• 关键词: Bone Resorption; Cells; Collagen; Computer Retrieval of Information on Scientific Projects Database; Funding; Gelatinase B; Grant; Human; Institution; Knowledge; Longitudinal Studies; Matrix Metalloproteinases; Osteoclasts; Periodontal Diseases; Pilot Projects; Porphyromonas gingivalis; Process; Reporting; Research; Research Personnel; Resources; Role; Site; Source; Staging; United States National Institutes of Health; bone; human MMP14 protein; insight; migration; monocyte; novel; osteoclastogenesis; pathogen

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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 破骨细胞是负责骨吸收的多核且高度运动的细胞。据报道，基质金属蛋白酶（MMP）对于促进破骨细胞迁移到骨吸收位点至关重要。 迄今为止，关于牙周病原体是否以及如何在分化破骨细胞生成细胞的各个阶段对迁移能力有直接影响的知识差距。 这项研究的总体目的是确定卟啉症牙龈（P. gingivalis）（一种主要的牙周病原体）在调节胶原蛋白降解和MMP-9和MMP-14表达中的作用和机制。 中心假设是，牙龈疟原虫可以通过刺激人类单核细胞和前骨细胞前的MMP表达和激活来增强胶原蛋白降解能力，从而促进骨质质发生细胞的迁移能力。 有三个特定的目的：1。确定牙龈疟原虫的培养上清液是否会增强人类前骨前核细胞中的胶原蛋白降解能力。 2。确定牙龈假单胞菌培养上清液对单核细胞和前骨前细胞中MMP-9和MMP-14激活和表达的影响。 3。确定MMP在牙龈疟原虫诱导的ost骨前和单核细胞迁移中的作用。 这些初步研究将提供重要信息，以进一步研究MMP在破骨细胞迁移，分化和功能中的作用。 从长远来看，这项研究将为牙周病原体促进破骨细胞迁移的机制提供重要的见解，并将有助于鉴定牙周疾病期间骨骼降解过程的新型靶向分子。