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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 破骨细胞是一种多核的高运动性细胞，负责骨吸收。基质金属蛋白酶（MMPs）已被报道是促进破骨细胞迁移到骨吸收部位的关键。 牙周致病菌是否以及如何直接影响破骨细胞分化的各个阶段的迁移能力，至今仍是一个知识空白。 本研究的总体目标是确定牙龈卟啉单胞菌（P. gingivalis）（一种主要的牙周病原体）在调节破骨细胞两个分化阶段（单核细胞和前破骨细胞）中胶原降解以及MMP-9和MMP-14表达方面的作用和机制。 中心假设是牙龈卟啉单胞菌可以通过刺激人单核细胞和前破骨细胞中MMP的表达和活化来增强胶原降解能力，从而促进破骨细胞生成细胞的迁移能力。 具体目标有三：1。确定牙龈卟啉单胞菌培养上清是否增强人前破骨细胞的胶原降解能力。 2.研究牙龈卟啉单胞菌培养上清对单核细胞和前破骨细胞中MMP-9和MMP-14活化和表达的影响。3.探讨基质金属蛋白酶在牙龈卟啉单胞菌诱导破骨细胞和单核细胞迁移中的作用。 这些初步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，这项研究将提供重要的见解牙周病原体促进破骨细胞迁移的机制，并将有助于确定新的靶向分子的骨降解过程中牙周疾病。