MMP-9调控MMP-2在小鼠根尖周炎骨质破坏中的研究

MMP-9 is closely related to oral inflammation. Nevertheless, the specific function of MMP-9 during each stage of oral inflammation as well as its mechanism is not well understood. Our previous studies found that in the experimentally induced apical periodontitis, severer inflammation occurred in MMP-9 knockout mice compared with wild type mice. Also, the pathology phenomenon of alveolar bone destruction was even more evident in MMP-9 knockout mice compared with wild type mice. Besides, we found that there was more MMP-2 expression in MMP-9 knockout mice compared with wild type mice. We proposed that MMP-9 inhibits MMP-2 expression by activating TGF-β1/SMAD2/3 signaling pathway. The phosphorylated SMAD2/3 bind to MMP-2 promoter thus regulates MMP-2 expression. The aims of this study are to study the role of MMP-9 in different stages of mouse apical periodontitis; to make clear the relationship between MMP-9 and osteogenesis/osteoclasia, apoptosis/cell proliferation; and to explore the complicated functional mechanism between MMP-2 and MMP-9. These will be achieved by performing cytological, histological, and molecular biological experiments, comparing the characteristics between MMP-9 knockout mice and wild type mice, and focusing on the regulation mechanism between MMP-9 and MMP-2 in mouse apical periodontitis. This research will give new clues to the prevention and treatment of apical periodontitis.

MMP-9与口腔炎症的发生密切相关，但其在口腔炎症各个阶段中发挥的具体作用及其机制尚未明确。本课题组前期研究发现，相对于野生型小鼠，MMP-9基因敲除型小鼠在实验诱导性根尖周炎中出现更加严重的炎症反应以及根尖周骨质破坏，研究同时发现后者根尖周炎病损区MMP-2的表达水平增高。本研究组推测，MMP-9可能通过激活TGF-β1/SMAD2/3抑制MMP-2的表达，磷酸化的SMAD2/3可直接作用于Mmp-2启动子，以调控Mmp-2的转录，影响根尖周炎病损区骨质的形成。因此，本研究拟在小鼠根尖周炎模型基础上，结合体外细胞实验，运用组织学、细胞学以及分子生物学等方法，①研究MMP-9在根尖周炎不同阶段骨质破坏中的作用；②探索MMP-9在根尖周炎过程同成骨/破骨、细胞凋亡/增殖等生物学现象之间的关系；③明确MMP-2和MMP-9之间相互作用的分子机制，为临床上对根尖周炎的防治提供实验基础和理论依据。

MMP-9与口腔炎症的发生密切相关，但其在口腔炎症各个阶段中发挥的具体作用及其机制尚未明确。本课题组前期研究发现，相对于野生型小鼠，MMP-9基因敲除型小鼠在实验诱导性根尖周炎中出现更加严重的炎症反应以及根尖周骨质破坏。本研究在小鼠根尖周炎模型基础上，结合体外细胞实验，运用组织学、细胞学以及分子生物学等方法，1研究MMPs和TIMPs在根尖周炎不同阶段的表达水平;2探索MMP-9在根尖周炎过程同炎症、成骨/破骨等生物学现象之间的关系，为临床上对根尖周炎的防治提供实验基础和理论依据。本研究发现MMPs和TIMPs在小鼠根尖周炎进展过程中的表达呈现不同程度相关性。在LPS刺激下,抑制了MMP9基因表达的MC3T3细胞中炎症因子IL-1β、TNF-α、MMP2，破骨因子RANKL均明显高于对照组及MMP9过表达组，与对照组相比较，MMP9过表达组炎症因子及破骨因子减少，而OPG、OC表达量增加。 本研究支持及验证了MMP9具有抗炎这一观点，为临床根尖周炎的靶向治疗提供了新的分子学依据。