随着中国社会老龄化日益加重，骨质疏松性骨折不仅是棘手的医学难题，也成为重要的公共卫生问题。间充质干细胞（MSC）具有很强的成骨分化潜力，体内能够促进骨折修复，但临床应用存在不少缺陷。鉴于MSC促进骨折愈合作用主要来源于局部旁分泌细胞因子，我们提出如下假说：促进外源性MSC旁分泌因子（HIF1α、VEGF、IGF1和TGF-β等）靶向作用于骨折局部，也能够显著促进骨质疏松骨折愈合和骨代谢改建。本研究拟以外源性细胞因子模拟MSCs旁分泌成骨微环境，以四环素作为骨组织的靶向基团，纳米PLGA作为载体材料，并将MSCs旁分泌因子包载入纳米载体内核，构建新型Tet-PLGA骨靶向纳米缓释体系，通过外周血液循环实现骨折区域精准主动靶向递送，促进骨折愈合和骨代谢改建，并借此探索旁分泌细胞因子促进骨质疏松骨折愈合的分子机制以及信号通路研究，为骨质疏松骨折治疗的临床实践提供基础实验依据。

With the increasing aging of Chinese society, osteoporosis fracture is not only a difficult medical problem, but also an important public health problem.Mesenchymal stem cells (MSC) have strong potential of osteogenic differentiation and can promote bone repair process in vivo, but there are many defects in clinical application.Since the promotion of fracture healing by MSC is mainly derived from paracrine cytokines, we propose the following hypothesis: promoting exogenous MSC paracrine factors (HIF1α, VEGF, IGF1, and TGF-β, etc.) on the local fracture could enhance osteoporosis fracture healing and bone metabolic remodeling.In this study, exogenous cytokines are used to simulate the paracrine osteogenic micro-environment of MSCs, tetracycline is used as the targeted group of bone tissue, and PLGA is used as the carrier to construct a new Tetracycline -PLGA bone targeted nano control-release system. MSC paracrine factors are loaded into the kernel of nano-meter carrier, in order to realize active targeted delivery to the fracture area promoting osteoporosis fracture healing, and to explore the molecular mechanism and signal pathway of paracrine cytokine as well as providing basic experiment basis in the treatment of osteoporosis fracture of for clinical practice.