人脂肪干细胞（hASCs）是骨组织工程理想的细胞来源，NF-κB作为关键的信号通路参与干细胞成骨分化，但其上游调控因素及相关信号分子尚未明确。核纤层蛋白相关多肽LAP2α已被证实在干细胞增殖分化中发挥作用。项目组前期研究发现，敲低LAP2α通过激活NF-κB通路抑制hASCs成骨分化，该激活作用可能由STAT3参与介导；故提出“LAP2α-STAT3-NF-κB信号轴在hASCs成骨分化中发挥重要调控作用”的假说。本项目拟采用基因过表达和siRNA干扰技术检测LAP2α对hASCs体内外成骨分化的影响；通过高通量测序、蛋白组学及染色质免疫共沉淀鉴定LAP2α与STAT3及NF-κB的作用关系；并通过阻断和激活相关通路，验证LAP2α-STAT3-NF-κB轴调控成骨过程中功能上的逻辑关系。本项目的成功实施，将为在分子水平提高hASCs成骨分化能力提供理论基础，为骨组织工程提供新的研究思路。

hASCs (human adipose-derived stem cells) are one of the ideal seed cells for bone tissue engineering. NF-κB is one of the key signaling pathways involved in the osteogenic differentiation of stem cells. However, upstream factors and related molecules that control the functions of NF-κB are still unknown. As a non-membrane-associated isoform of the mammalian LAP2 gene, LAP2α (lamina-associated polypeptide 2α) has been proved to play a critical role in the regulation of adult stem cell function. In our previous work, we found that LAP2α knockdown resulted in an impairment of osteogenic differentiation of hASCs via the activation of NF-κB signaling pathway. This activation may be mediated by STAT3 (signal transducer and activator of transcription 3), but the specific regulatory mechanism remains to be clarified. Therefore, we propose the hypothesis that LAP2α-STAT3-NF-κB signaling axis plays an important role in the osteogenic differentiation of hASCs. In this study, we aim to investigate the effects of LAP2α on the osteogenic differentiation of hASCs through genetic depletion or overexpression with lentiviral strategy. Additionally, high-throughput sequencing, proteomic identification, and chromatin immunoprecipitation are used to explore the interations among LAP2α, STAT3 and NF-κB. Furthermore, by blocking and activating the relevant pathways, we want to further clarify the regulatory effects of the whole LAP2α-STAT3-NF-κB signaling axis on the osteogenic differentiation of hASCs. Through this comprehensive study, it will not only provide a mechanistic link of LAP2α to osteogenic differentiation of hASCs, but also make a solid foundation for the development of new therapeutic approaches for hASCs-based cell therapy and bone tissue engineering.