老年患者成骨能力及骨再生潜能下降，使其颌面部骨缺损的近远期修复效果面临巨大挑战。我们最新研究发现间断性PTH(1-34)治疗能够正向调控老年骨髓间充质细胞（BMSCs）成骨分化，促进老年机体血管化骨再生，同时能够引起BMSCs内以及其来源的外泌体中miR-199a表达显著下调。因此，推测miRNA-199a-mRNAs调控轴可能参与了PTH(1-34)正向调控老年机体骨再生修复的过程。为进一步证实该推测并探索其具体的分子机制，本研究拟通过体内和体外实验，应用分子生物学及生物信息学技术、结合iTRAQ定量蛋白质谱技术、基因沉默或过表达等干预手段，明确BMSCs来源的外泌体miR-199a介导PTH (1-34)对老年机体骨形成和骨吸收的调控作用，揭示miRNA-199a-mRNAs调控轴的具体作用机制。本研究结果将为完善老年机体骨再生修复的机制提供有效证据，并有望为临床治疗提供新的策略。

Aging attenuates bone regeneration potential and osteogenic ability in elderly patients, which may consequently make a great challenge in short-term and long-term restoration of maxillofacial bone defect. Recently, we found the positive regulation of PTH (1-34) on the osteogenic differentiation potential of aged bone marrow mesenchymal cells (BMSCs) and rapid vascularized bone regeneration. Meanwhile, PTH (1-34) could significantly decreased miR-199a level both in BMSCs and BMSCs-derived exosomes. Therefore, we speculated that miR-199a-mRNAs may be involved in promoting bone regeneration regulated by PTH (1-34) in aging. Molecular biology and bioinformatics technology, together with iTRAQ labeling proteomic analysis and gene silencing or overexpression method will be applied in vivo and in vitro to further confirm this speculation and to explore the mechanisms of PTH(1-34) on regulating bone formation and resorption in aging through BMSCs-derived exosomal miR-199a. Furthermore, the way of miR-199a-mRNAs regulated by PTH (1-34) will be validated. This study provides an important theoretical basis for clarifying the etiology of aging bone regeneration and a new strategy for clinic treatment.