Mesenchymal stem cells overexpressing Ihh promote bone repair

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• 作者：Shasha Zou (1)
  Tingting Chen (1)
  Yanan Wang (1)
  Ruhui Tian (1)
  Lingling Zhang (2)
  Pingping Song (1)
  Shi Yang (1)
  Yong Zhu (1)
  Xizhi Guo (2)
  Yiran Huang (1)
  Zheng Li (1)
  Lixin Kan (3) (4)
  Hongliang Hu (1)
  
  1. Renji Hospital ; School of Medicine ; Shanghai Jiao Tong University ; 845 Lingshan Road ; Shanghai ; 200135 ; China
  2. BIO-X Center ; Shanghai Jiao Tong University ; 55 Guangyuan West Road ; Shanghai ; 200240 ; China
  3. Department of Pathophysiology ; School of Basic Medicine ; Anhui Medical University ; 81 Meishan Road ; Hefei ; Anhui ; 230032 ; China
  4. Feinberg School of Medicine ; Northwestern University ; 303 East Chicago Avenue ; Chicago ; IL ; 60611 ; USA
  
• 关键词：Indian hedgehog (Ihh) ; Chondrogenesis ; Osteogenesis ; Angiogenesis ; Mesenchymal stem cells (MSCs) ; Tissue engineering
• 刊名：Journal of Orthopaedic Surgery and Research
• 出版年：2014
• 出版时间：December 2014
• 年：2014
• 卷：9
• 期：1
• 全文大小：2,278 KB
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• 刊物主题：Orthopedics; Surgical Orthopedics;
• 出版者：BioMed Central
• ISSN：1749-799X

文摘

Background Indian hedgehog (Ihh) signaling pathway is known to play key roles in various aspects of normal endochondral bone development. This study tested the potential roles of high Ihh signaling in the context of injury-induced bone regeneration. Methods A rabbit tibia defect model was established to test the effects of the implant of Ihh/mesenchymal stem cells (MSCs)/scaffold complex. Computed tomography (CT), gross observation, and standard histological and immunohistological techniques were used to evaluate the effectiveness of the treatment. In vitro studies with MSCs and C3H10T1/2 cells were also employed to further understand the cellular and molecular mechanisms. Results We found that the implanted Ihh/MSCs/scaffold complex promoted bone repair. Consistently, in vitro study found that Ihh induced the upregulation of chondrocytic, osteogenic, and vascular cell markers, both in C3H10T1/2 cells and MSCs. Conclusions Our study has demonstrated that high Ihh signaling in a complex with MSCs enhanced bone regeneration effectively in a clinically relevant acute injury model. Even though the exact underlying mechanisms are still far from clear, our primary data suggested that enhanced chondrogenesis, osteogenesis, and angiogenesis of MSCs at least partially contribute to the process. This study not only has implications for basic research of MSCs and Ihh signaling pathway but also points to the possibility of direct application of this specific paradigm to clinical bone repair.