Wang Guangxi, Yan Jinglong, Zhang Hao, Massey Patrick, Alexander J Steven, Kevil Christopher G, Barton Shane, Dong Yufeng
Department of Orthopedic Surgery, The Second Affiliated Hospital, Harbin Medical University, Heilongjiang, China.
Department of Orthopedic Surgery, LSU Health Sciences Center, Shreveport, LA, USA.
J Orthop Translat. 2021 Oct 22;31:26-32. doi: 10.1016/j.jot.2021.09.007. eCollection 2021 Nov.
Following traumatic bone loss or removal of bone tumors, the failure of bone allograft transplantation for large bone defect repair remains a significant problem in orthopedics. Therefore, new strategies that can efficiently enhance allograft healing and long-term incorporation are critically needed.
In this study, we first injected Notch-activating Jagged1 peptide to mice and then isolated bone marrow tissues and cells for proliferation and differentiation assays. Femur bone allograft surgery was also performed in Jagged1 pre-treated mice, and bone defect healing process were monitored by histology, Micro-CT and biomechanical testing.
Our results showed that Jagged1 therapeutic injection is sufficient to maximally activate Notch and promote bone marrow stromal cell proliferation , while no effects on bone structure were observed. More importantly, Jagged1 pre-treatment significantly promoted bone callus formation and increased bone mechanical strength during allograft healing in a femur bone defect mouse model.
This study reveals that Notch activation can be induced by injection of Jagged1 peptide for expansion of local native stromal cells that will significantly enhance bone callus formation.
The clinical uses of this therapeutic strategy would be immediately applicable for chronic long bone defect repair. More importantly, this devised strategy for expansion of endogenous BMSCs can also be applied to enhance other tissue and organ repair.
在创伤性骨丢失或骨肿瘤切除后，同种异体骨移植修复大的骨缺损失败仍然是骨科领域的一个重大问题。因此，迫切需要能够有效促进同种异体骨愈合和长期整合的新策略。
在本研究中，我们首先给小鼠注射Notch激活肽Jagged1，然后分离骨髓组织和细胞进行增殖和分化分析。对经Jagged1预处理的小鼠也进行了股骨同种异体骨移植手术，并通过组织学、显微CT和生物力学测试监测骨缺损愈合过程。
我们的结果表明，Jagged1治疗性注射足以最大程度地激活Notch并促进骨髓基质细胞增殖，同时未观察到对骨结构的影响。更重要的是，在股骨骨缺损小鼠模型中，Jagged1预处理显著促进了同种异体骨愈合过程中的骨痂形成并提高了骨机械强度。
本研究表明，注射Jagged1肽可诱导Notch激活，以扩增局部天然基质细胞，这将显著增强骨痂形成。
这种治疗策略的临床应用可立即用于慢性长骨缺损修复。更重要的是，这种设计的扩增内源性骨髓间充质干细胞的策略也可用于增强其他组织和器官的修复。
