title: Mesenchymal stem cells overexpressing Ihh promote bone repair.
abstract: 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.
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. zoushashash@126.com.
authors.forename: Shasha
authors.initials: S
authors.lastname: Zou
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. 924587405@139.com.
authors.forename: Tingting
authors.initials: T
authors.lastname: Chen
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. medicaln@126.com.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. tianruhui@gmail.com.
authors.forename: Ruhui
authors.initials: R
authors.lastname: Tian
authors.affiliation: BIO-X Center, Shanghai Jiao Tong University, 55 Guangyuan West Road, Shanghai, 200240, China. 282286983@qq.com.
authors.forename: Lingling
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. spiong1230@163.com.
authors.forename: Pingping
authors.initials: P
authors.lastname: Song
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. yangshi_526@163.com.
authors.forename: Shi
authors.initials: S
authors.lastname: Yang
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. sxl7230@gmail.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: BIO-X Center, Shanghai Jiao Tong University, 55 Guangyuan West Road, Shanghai, 200240, China. xzguo2005@sjtu.edu.cn.
authors.forename: Xizhi
authors.initials: X
authors.lastname: Guo
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. 805214151@qq.com.
authors.forename: Yiran
authors.initials: Y
authors.lastname: Huang
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. doc.zheng.li@gmail.com.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, School of Basic Medicine, Anhui Medical University, 81 Meishan Road, Hefei, Anhui, 230032, China. l-kan@northwestern.edu.|Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, IL, 60611, USA. l-kan@northwestern.edu.
authors.forename: Lixin
authors.initials: L
authors.lastname: Kan
authors.affiliation: Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai, 200135, China. hongliang_hu67@hotmail.com.
authors.forename: Hongliang
authors.initials: H
authors.lastname: Hu
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D002460:Cell Line; D015870:Gene Expression / Q000502:physiology; D053823:Hedgehog Proteins / Q000096:biosynthesis / Q000502:physiology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D011817:Rabbits; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013977:Tibia / Q000254:growth & development; D054457:Tissue Scaffolds
chemical_list: D053823:Hedgehog Proteins