title: Involvement of Indian hedgehog signaling in mesenchymal stem cell-augmented rotator cuff tendon repair in an athymic rat model.
abstract: BACKGROUND
  Bone marrow aspirate has been used in recent years to augment tendon-to-bone healing, including in rotator cuff repair. However, the healing mechanism in cell-based therapy has not been elucidated in detail.
  
  
  METHODS
  Sixteen athymic nude rats were randomly allocated to 2 groups: experimental (human mesenchymal stem cells in fibrin glue carrier) and control (fibrin glue only). Animals were sacrificed at 2 and 4 weeks. Immunohistochemical staining was performed to evaluate Indian hedgehog (Ihh) signaling and SOX9 signaling in the healing enthesis. Macrophages were identified using CD68 and CD163 staining, and proliferating cells were identified using proliferating cell nuclear antigen staining.
  
  
  RESULTS
  More organized and stronger staining for collagen II and a higher abundance of SOX9+cells were observed at the enthesis in the experimental group at 2 weeks. There was significantly higher Gli1 and Patched1 expression in the experimental group at the enthesis at 2 weeks and higher numbers of Ihh+cells in the enthesis of the experimental group vs control at both 2 weeks and 4 weeks postoperatively. There were more CD68+cells localized to the tendon midsubstance at 2 weeks compared with 4 weeks, and there was a higher level of CD163 staining in the tendon midsubstance in the experimental group than in the control group at 4 weeks.
  
  
  CONCLUSIONS
  Stem cell application had a positive effect on fibrocartilage formation at the healing rotator cuff repair site. Both SOX9 and Ihh signaling appear to play an important role in the healing process.
authors.affiliation: Department of Orthopaedic Surgery, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China.
authors.forename: Jian-Chun
authors.initials: JC
authors.lastname: Zong
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Mosca
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Ryan M
authors.initials: RM
authors.lastname: Degen
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Lebaschi
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Camila
authors.initials: C
authors.lastname: Carballo
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Carbone
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Guang-Ting
authors.initials: GT
authors.lastname: Cong
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Liang
authors.initials: L
authors.lastname: Ying
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA.
authors.forename: Xiang-Hua
authors.initials: XH
authors.lastname: Deng
authors.affiliation: The Hospital for Special Surgery, New York, NY, USA. Electronic address: rodeos@hss.edu.
authors.forename: Scott A
authors.initials: SA
authors.lastname: Rodeo
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D002452:Cell Count; D024043:Collagen Type II / Q000378:metabolism; D051445:Fibrocartilage; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000737:chemistry; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D000072081:Patched-1 Receptor / Q000378:metabolism; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000032:analysis; D017006:Rotator Cuff / Q000378:metabolism*; D055758:SOX9 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D014945:Wound Healing; D000071676:Zinc Finger Protein GLI1 / Q000378:metabolism; D000098902:CD163 Antigen; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D024043:Collagen Type II; D053823:Hedgehog Proteins; D000072081:Patched-1 Receptor; D011956:Receptors, Cell Surface; D055758:SOX9 Transcription Factor; D000071676:Zinc Finger Protein GLI1; D000098902:CD163 Antigen; C539355:CD68 protein, rat; D000097382:CD68 Molecule; C498521:Gli1 protein, rat; C000606239:Ptch1 protein, rat
keywords: Indian hedgehog; enthesis; repair; rotator cuff; sox9; stem cell