title: EGR1 induces tenogenic differentiation of tendon stem cells and promotes rabbit rotator cuff repair.
abstract: OBJECTIVE
  The rate of healing failure after surgical repair of chronic rotator cuff tears is considerably high. The aim of this study was to investigate the function of the zinc finger transcription factor early growth response 1 (EGR1) in the differentiation of tendon stem cells (TSCs) and in tendon formation, healing, and tendon tear repair using an animal model of rotator cuff repair.
  
  
  METHODS
  Tenocyte, adipocyte, osteocyte, and chondrocyte differentiation as well as the expression of related genes were determined in EGR1-overexpressing TSCs (EGR1-TSCs) using tissue-specific staining, immunofluorescence staining, quantitative PCR, and western blotting. A rabbit rotator cuff repair model was established, and TSCs and EGR1-TSCs in a fibrin glue carrier were applied onto repair sites. The rabbits were sacrificed 8 weeks after repair operation, and tissues were histologically evaluated and tenocyte-related gene expression was determined.
  
  
  RESULTS
  EGR1 induced tenogenic differentiation of TSCs and inhibited non-tenocyte differentiation of TSCs. Furthermore, EGR1 promoted tendon repair in a rabbit model of rotator cuff injury. The BMP12/Smad1/5/8 signaling pathway was involved in EGR1-induced tenogenic differentiation and rotator cuff tendon repair.
  
  
  CONCLUSIONS
  EGR1 plays a key role in tendon formation, healing, and repair through BMP12/Smad1/5/8 pathway. EGR1-TSCs is a promising treatment for rotator cuff tendon repair surgeries.
authors.affiliation: Department of Orthopaedics, Southwest Hospital, Third Military Medical University, Chongqing, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Tao
authors.forename: Junpeng
authors.initials: J
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.forename: You
authors.initials: Y
authors.lastname: Zhou
authors.forename: Kanglai
authors.initials: K
authors.lastname: Tang
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D008297:Male; D009928:Organ Specificity; D011817:Rabbits; D017006:Rotator Cuff / Q000473:pathology; D000070636:Rotator Cuff Injuries; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013708:Tendon Injuries / Q000473:pathology / Q000628:therapy*; D014945:Wound Healing
chemical_list: D019485:Bone Morphogenetic Proteins; D051766:Early Growth Response Protein 1; D051785:Smad Proteins