骨髓间充质干细胞(MSCs)向成骨细胞分化的潜能降低是多发性骨髓瘤骨病重要的病因之一，但具体机制和调控分子尚不清楚。我们前期结果显示骨髓瘤骨病患者的MSCs向成骨细胞分化潜能降低伴随转录因子RUNX1和紧密连接蛋白TJP1、CLDN5和OCLN的表达减少。体外实验进一步表明RUNX1转录调节TJP1并影响MSCs成骨分化能力。据此，我们提出RUNX1可能通过转录水平调控紧密连接蛋白影响MSCs的成骨分化，并在骨髓瘤骨病的发生发展中起关键作用。本项目拟揭示RUNX1与紧密连接蛋白和MSCs成骨分化与骨髓瘤骨病在临床上的相关性，阐明RUNX1转录调控紧密连接蛋白的分子机制和相关通路。此外，本项目拟利用多肽药物筛选库发掘并验证RUNX1在骨髓瘤骨病中的临床应用价值。本研究有望揭示一种影响MSCs分化的新机制，并为临床转化和治疗提供理论基础和靶点参考。

MSCs differentiation disability into osteoblasts is one of important reasons for myeloma bone disease. However, the mechanism and regulators involved are still unclear. Our preliminary experiment showed that differentiation potential of MSCs into osteoblasts in myeloma bone disease patients decreased and the expression of RUNX1, TJP1, CLDN5 and OCLN was down-regulated. Furthermore, we found that TJP1 restrained MSCs osteoblasts differentiation possibility regulated by RUNX1 transcriptionally. Thus, our hypothesis is that RUNX1 transcriptionally regulates tight junction proteins, which will induce osteogenic differentiation defect of MSCs in myeloma bone disease. Our proposal will explore the mechanism of RUNX1 regulates tight junction proteins in MSCs of myeloma bone disease and relationship between the RUNX1 and tight junction proteins in myeloma bone disease. Moreover, we will investigate and validate the clinical application of RUNX1 in myeloma bone disease by using polypeptide drug screening library. In summary, this study will clarify a new mechanism of differentiation of MSCs into osteoblasts, and its role in the pathogenesis of myeloma bone disease, which will provide new ideas and biomarkers for the diagnosis and treatment of myeloma bone disease.