动态机械力学刺激Hh信号促进OPLL来源的肌腱干细胞异常成骨分化的研究

后纵韧带骨化症（OPLL）逐渐成为我国常见的脊柱退行性疾病，近年来后纵韧带中的间叶干细胞（MSCs）错误分化被认为是发病主要原因之一。既往的实验已经证实间叶干细胞存在于后纵韧带骨化中并且具有较高的成骨分化能力。同时，与脊柱骨化韧带同胚层来源的脂肪 MSCs 也具有较高的成骨分化潜能。另一方面，在对MSCs进行动态机械力学刺激后，发现适当的动态力学刺激可以促进其成骨分化。我们前期试验发现OPLL患者后纵韧带中存在SCX+/TPPP3+肌腱干细胞，其与间叶干细胞一样都有一定成骨能力与受力学调控的特性。但脊柱韧带中肌腱干祖细胞是否因为受到机械力学刺激后导致错误成骨分化尚未得知。本研究结合课题组前期单细胞测序结果，利用动态机械拉力、荧光免疫染色及骨化小鼠模型等技术和材料，进一步探寻后纵骨化韧带中干细胞错误分化的机制以及动态机械力学对其的影响，为临床治疗OPLL提供实验基础和治疗方案。

OPLL is one of the most common spinal degenerative diseases in China. Misdifferentiation of mesenchymal stem cells (MSCs) in the posterior longitudinal ligament is considered to be one of the main causes of OPLL. Previous experiments have confirmed that mesenchymal stem cells exist in the posterior longitudinal calcified ligament and have a high ability of osteogenic differentiation. At the same time, adipose MSCs from the same dermal origin as spinal ossified ligaments also have higher osteogenic differentiation potential, and SCX +/ TPPP3 + tendon stem cells are also present. On the other hand, after dynamic mechanical stimulation of MSCs, it was found that appropriate dynamic mechanical stimulation could promote osteogenic differentiation of MSCs. However, are all stem cells in the spinal ligaments misdifferentiated? Are the stem progenitor cells in the spinal ligaments misdifferentiated due to mechanical stimulation? None of the above is known. In this study, single-cell sequencing, dynamic mechanical tension, fluorescence immunostaining and ossification mouse model were used to further explore the mechanism of stem cell misdifferentiation in OPLL and the influence of dynamic mechanical mechanics on it, so as to provide an experimental basis and treatment plan for clinical treatment of OPLL ossification.