老年黄韧带骨化症（OLF）是非瘤性老年成骨现象，探索其成骨机制有利于防治OLF和骨质疏松症（OP）。我们前期应用基因芯片在OLF组织中筛选出一个显著过表达且具有物种同源性的lncRNA-SNHG4；确定了其全长并定位在细胞浆和细胞核；同时发现SNHG4在OLF组织，间充质干细胞（MSCs）及前成骨细胞的成骨分化过程中过表达；而在卵巢去势及鼠尾悬吊骨质疏松小鼠模型的股骨组织中低表达；沉默hMSCs中SNHG4抑制成骨分化。本次申报：1、在细胞和动物水平阐明SNHG4在成骨分化、OLF和OP发病中的作用；2、揭示SNHG4促进成骨的分子网络及异常表达的机理；3、检测SNHG4在患者OLF组织、OP骨组织及血清中的水平，揭示其与疾病的相关性；为SNHG4作为OLF和OP的诊断标志物及治疗靶点提供理论和实验依据。

The consequence of ossification of ligamentum flavum (OLF) is non-tumor bone formation in elderly. To investigate the relevant mechanism is beneficial to the prevention and treatment of OLF and osteoporosis (OP). We have identified lncRNA-SNHG4 that is over-expressed and has homology in human and mouse in OLF tissue by microarray assay. We have also identified the sequence of this molecule and found it is localized in the cytoplasm and nucleus. In addition, lncRNA-SNHG4 was found to be over-expressed in OLF tissues and the process of osteogenic differentiation of both the human mesenchymal stem cells (hMSCs) and the preosteoblasts, however, it is reduced in the femurs of ovariectomized (OVX) and hindlimb-unloaded mice models. Silencing SNHG4 in hMSCs inhibits osteogenic differentiation. We will further investigate the role of SNHG4 in osteogenic differentiation, OLF and OP on the cellular level and with the use of animal models, and identify the pathway through which SNHG4 promotes osteogenesis and the mechanism that SNHG4 dys-expressed. We will also detect the level of SNHG4 in OLF tissue, bone tissue of OP and serum from patients to correlate this molecule with those disorders, providing experimental evidence for SNHG4 as a diagnostic marker and therapeutic target for OLF and OP.