MBMSCs对颌骨骨质疏松骨代谢的意义及其关键miRNA的筛选与功能鉴定

Mandibular osteoporosis (MOP) is one of clinical manifestations of osteoporosis (OP). Despite being seemingly similar to long bone in the body, mandible serve distinct functions and demonstrate discrete responses to developmental, mechanical, and homeostatic stimuli. Several growth factors receptors, and associated signaling cascades play distinct roles in the craniofacial vs. axial and appendicular skeleton.There appears to be a correlation between mandibular bone density and osteoporosis. Mandibles lose significantly less trabecular bone and bone mineral density at a lower rate than tibiae primary spongiosa after ovariectomy, suggesting different homeostatic mechanisms of the two bones. miRNA is an important molecular switch in stem cell differentiation phenotype, which participate in various physiological and pathological processes. The preliminary study found that miRNA negatively regulate the expression of target gene at post transcriptional level during OP, changing BMSCs phenotype. However, until now there is no report that whether the occurrence of MOP is due to spcecial miRNA interference which change MBMSCs differentiation phenotype . It is also unknown for us that whether miRNA can prevent the occurrence of MOP or reverse MOP development. Firstly,we aim to making clear whether MBMSCs affect mandible bone metabolism by establising the MOP mouse model. secondly, our team plan to study the function and molecular mechanism of miRNA, which lead to abnormal characteristics of MBMSCs by the miRNA gene chip technology and biological information.Finally, we observe the treatment effect of MOP mouse model by injecting modified MBMSCs with spcecial miRNA . This project aims to explore the expression profile and function of key miRNA in the MBMSCs of MOP and provides threads and methods for new strategies of mandible osteoporosis treatment and improvement, then it can provide new insights into prevention and treatment of loss of the jaw bones .

颌骨骨质疏松（MOP）是全身骨质疏松（OP）的局部表现之一，颌骨无论是组织来源与发育、成骨方式，还是成骨基因的表达、对细胞因子及信号通路的反应性等均与长骨有明显区别，导致了MOP的程度、速度和时间与长骨OP存在明显差异。miRNA是干细胞分化表型重要分子开关，参与各种生理病理过程。然而，MOP的发生是否因miRNA干扰MBMSCs分化表型？改变miRNA是否可阻止甚至逆转MOP的发生发展等系列问题未见报道。本课题拟通过 MOP小鼠模型，明确 MOP中MBMSCs是否影响颌骨代谢；其次，通过miRNA芯片技术和生物学信息，研究导致MBMSCs异常特性的关键miRNA的功能作用及其分子机制；最后，将miRNA修饰后的MBMSCs局部注射MOP动物模型观察治疗效果。本项目旨在探索MOP发病过程中MBMSCs关键miRNA表达谱及其功能作用，并为MOP治疗提供新策略。

颌骨骨质疏松是造成颌骨骨丢失和骨质质量快速下降的主要危险因素。此病的发生主要是由于细胞更新和骨再生的平衡破坏,颌骨骨髓间充质干细胞(MBMSCs)具有自我更新能力和多向分化能力，在颌骨骨质疏松症的发病中起着关键作用。miRNA通过与靶基因mRNA 3′-非翻译区结合沉默靶基因的表达，从而在个体发育、细胞增殖和多种疾病中发挥着重要的调控作用。本项目你在以往对绝经后骨质疏松研究的基础上，构建绝经后小鼠颌骨骨质疏松模型，结合体内和体外实验，综合形态学、分子生物学、表观遗传学等方法，观察颌骨骨质疏松大鼠模型中MBMSCs功能和作用变化，明确其在颌骨骨质疏松症发病中的重要作用，并通过miRNA微阵列芯片技术寻找出发病过程中可能发挥作用的特异性miRNA，探究关键miRNA调控MBMSCs生物学特性从而影响骨质疏松症的发病机制。该项目旨在研究以关键miRNA为靶点逆转MBMSCs生物学性能，为预防和治疗颌骨骨质疏松提供新的思路和参考。