title: In vitro flexor tendon cell response to TGF-beta1: a gene expression study.
abstract: OBJECTIVE
  Adhesion formation around zone II flexor tendon repairs remains an important clinical challenge. Tendon healing is complex, and when uncontrolled it may lead to adhesion formation. Transforming growth factor-beta1 (TGF-beta1) is a multipotent growth factor known to be involved in wound healing and scar formation. It has also been shown to have a role in both tendon healing and adhesion formation.
  
  
  METHODS
  Uninjured rabbit flexor tendons were divided into endotenon, epitenon, and sheath cells and cultured separately. The in vitro effect of TGF-beta1 gene expression was determined on quiescent tendon cells using real-time polymerase chain reaction for collagen type 1, collagen type 3, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (t-PA).
  
  
  RESULTS
  Endotenon-derived cells showed a statistically significant down-regulation of collagen type I gene expression in response to TGF-beta1 compared with untreated endotenon cells and with both epitenon and sheath cells at a number of time points. However, endotenon cells showed an increase in collagen type 3 gene expression compared with untreated cells and epitenon cells. All cells showed a statistically significant increase in fibronectin in the later time points compared with the untreated cells. Endotenon-derived cells showed an early increase in PAI-1, whereas sheath cells showed a later increase.
  
  
  CONCLUSIONS
  We have shown that cells cultured from 3 separate parts of the flexor tendon-sheath complex respond in different ways when stimulated with TGF-beta1. The down-regulation of collagen types 1 and 3 in endotenon cells may give further insight into the effects of TGF-beta1 in tendon healing. Also, the upregulation of fibronectin and PAI-1, combined with a down-regulation of tissue plasminogen activator, could explain the association of TGF-beta1 with tendon adhesion formation. Treatments aimed at improving tendon healing and the prevention of adhesions may arise from modification of the effects of TGF-beta1.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Royal Free Hospital, London, UK. ben.klass@gmail.com
authors.forename: B R
authors.initials: BR
authors.lastname: Klass
authors.forename: K J
authors.initials: KJ
authors.lastname: Rolfe
authors.forename: A O
authors.initials: AO
authors.lastname: Grobbelaar
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics; D024061:Collagen Type III / Q000235:genetics; D015536:Down-Regulation; D005353:Fibronectins / Q000235:genetics; D015870:Gene Expression; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D016133:Polymerase Chain Reaction; D012313:RNA / Q000302:isolation & purification; D011817:Rabbits; D013710:Tendons / Q000166:cytology*; D010959:Tissue Plasminogen Activator / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D005353:Fibronectins; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; D012313:RNA; D010959:Tissue Plasminogen Activator