肌骨素介导的骨代谢调控机制及对骨质疏松性骨折的风险评估

As two closely related organs, musculoskeletal disorders severely affect human health. Therefore, the investigation of muscle-bone interaction becomes growing interest for medical research. Muscle derived Myostatin plays critical roles in skeletal muscle growth and its expression levels in serum are increased during age, suggesting Myostatin may also functions in bone metabolism. Osteoporotic fracture (OF) is one of the typical aging related diseases associated with a high incidence of disability. Both muscle and bone degeneration increase the risk of OF. However, whether the serum levels of Myostatin can be served as a risk marker for OF is poorly understood. In this study, we firstly detect the effect of Myostatin on osteoblast and osteoclast using cellular and molecular approaches. Subsequently, we will examine the serum levels of Myostatin and construct the correlation between Myostatin and Bone Mineral Density (BMD). In addition, the differential expression of Myostatin between OF patients and healthy group will be measured to further assess the association between serum Myostatin and occurrence of OF. Altogether, this project will provide insights into the developing of new methods and technologies in the early diagnosis and intervention of OF.

骨骼和肌肉是两类关系最为密切的器官，其损伤严重影响人类的健康，因此对骨和肌肉相互作用的研究逐渐成为医学研究的重点。肌细胞分泌的肌骨素（Myostatin）在肌肉生长过程中发挥着重要作用，血清中肌骨素的含量会随着年龄的增长而递增，暗示肌骨素可能对骨代谢产生影响。骨质疏松性骨折（OF）作为典型的老年性疾病具有很高的致残率，其发生与骨和肌肉老化密切相关，而肌骨素能否作为骨质疏松性骨折的风险标志物尚不清楚。因此，本项目拟首先结合细胞和分子生物学方法研究肌骨素对人成骨细胞及破骨前体细胞影响。在此基础上，以骨质疏松性骨折患者为研究对象，检测样本血清中肌骨素的含量和骨密度，构建肌骨素与骨密度之间的相关性。此外，我们还将分析对照组和OF组间肌骨素表达的差异性，进一步评估肌骨素与骨质疏松性骨折发生风险间的关系，为提高其诊断水平以及开发新的早期干预和预防的方法提供基础。

肌骨素是一种肌肉分泌因子主要负调控肌肉的生长，而对于肌骨素是否参与骨代谢调控至今未知。通过征集2个中国老年人队列样本（共6308人）进行整合性分析人体肌肉含量，血浆肌骨素水平和骨密度三者关系。研究发现血浆中总的肌骨素含量主要与人体肌肉含量显著相关；而血浆中成熟肌骨素相对含量（成熟/总肌骨素）在老年高骨密度人群中显著下调，且相对肌骨素含量与骨吸收标志物之间负相关。最终我们通过体外细胞实验进一步证实了肌骨素对于成骨前体细胞的增殖和分化有较强的抑制作用。本项目阐明了血浆中成熟肌骨素的相对含量与骨密度存在负相关，其潜在机制可能是通过抑制成骨/破骨细胞的增殖和分化有关。本研究深入了解了血浆肌骨素的作用，为临床应用提供有效的药物靶点。