Wnt信号通路对增龄性骨质疏松条件下颌骨骨髓间充质干细胞成骨分化的调控机制研究

Dental implant prosthesis is recognized as the first choice for restoration of missing teeth. Osseointegration is a key factor on affecting the dental implant success in the alveolar bone. Aging osteoporosis which presents decreased bone mineral density is significantly influence of psychological wound affect elder’s health. Poor combination of bone has become a serious problem plagued dental implant placement. Mesenchymal stem cell is a base of tissue regeneration, but the microenvironment effect the function of stem cells existed significant difference. Our previous studies have been successfully obtained MSCs from the jaw bone marrow (JBMMSCs), and confirmed in situ mandibular alveolar bone formation ability of MSCs to be significantly stronger than the bone marrow MSCs, and the Wnt signaling pathway has a significant effect in this process. But the role of the key signaling pathways and the molecular mechanisms in JBMMSCs is not clear during osteogenic differentiation and bone regeneration ability biased with aging. Therefore, the subject of the proposed research by system comparing the young and aging osteoporosis JBMMSC’s biological behavior. To confirm the effect of key signal molecular on Wnt signaling pathway. Our aim is to recovery the bone regeneration ability in osteoporosis microenvironment through the regulation of Wnt signaling pathway. And provide a theoretical basis for clinical dental implant placement in aging osteoporosis microenvironment.

口腔种植修复是治疗牙缺失的首选方案，而骨结合是种植是否成功的关键因素。增龄性骨质疏松引起的骨结合不佳已成为困扰老年人牙种植的严重问题。间充质干细胞是组织再生的基础，但不同组织来源干细胞功能存在差异、不同微环境可直接影响干细胞功能。我们前期已成功从颌骨获得MSCs，并证实颌骨MSCs的牙槽骨原位成骨能力显著强于骨髓MSCs，且Wnt信号通路在该过程中作用显著。但衰老微环境中Wnt信号通路在颌骨MSCs成骨分化及骨再生能力改变方面发挥作用的分子机制和作用规律尚不清楚，因此，本课题拟系统对比研究年轻和自然衰老骨质疏松来源的颌骨MSCs生物学行为差异，阐明Wnt信号通路在颌骨MSCs成骨分化中的调控机制和规律, 通过调控Wnt信号通路恢复颌骨MSCs骨再生能力，为提高增龄性骨质疏松患者种植牙骨结合提供理论依据。

口腔种植修复是治疗牙缺失的首选方案，而骨结合是种植是否成功的关键因素。增龄性骨质疏松引起的骨结合不佳已成为困扰老年人牙种植的严重问题。间充质干细胞是组织再生的基础，但不同组织来源干细胞功能存在差异，不同微环境可直接影响干细胞功能。我们前期已成功从颌骨获得MSCs，并证实颌骨MSCs的牙槽骨原位成骨能力显著强于骨髓MSCs，且Wnt信号通路在该过程中作用显著。但衰老性骨质疏松条件下Wnt信号通路在颌骨MSCs成骨分化及骨再生能力改变方面发挥作用的分子机制和作用规律尚不清楚。因此，本课题对年轻和自然衰老骨质疏松来源的颌骨MSCs生物学行为差异进行了研究，并对Wnt信号通路在颌骨MSCs成骨分化中的调控机制和规律进行了初步探索。研究结果显示，20月龄自然衰老大鼠其骨密度、骨小梁数目降低而骨小梁分离度增加（P＜0.05），表现出了明显的骨质疏松。衰老性骨质疏松条件下颌骨骨髓间充质干细胞增殖能力、成骨分化能力降低，Wnt信号通路相关分子Wnt3a、β-catenin、TCF4表达降低且差异显著（P＜0.05）。本研究对增龄性骨质疏松条件下Wnt信号通路对颌骨骨髓间充质干细胞成骨分化的调控机制进行了探索，为恢复颌骨MSCs骨再生能力，提高增龄性骨质疏松患者种植牙骨结合提供了理论依据。