title: Effect of several growth factors on canine flexor tendon fibroblast proliferation and collagen synthesis in vitro.
abstract: OBJECTIVE
  Growth factor delivery may be useful to accelerate the rate of tendon healing. Before in vivo use, however, the effects of growth factors on tendon cells need to be well characterized. The purpose of this study was to evaluate the effects of 4 growth factors on intrasynovial tendon fibroblast proliferation and collagen production in vitro. Our first hypothesis was that platelet-derived growth factor BB (PDGF-BB) and basic fibroblast growth factor (bFGF) would promote cell proliferation and collagen production. Our second hypothesis was that there would be a positive effect from the combination of PDGF-BB and bFGF.
  
  
  METHODS
  The growth factors PDGF-BB, bFGF, vascular endothelial growth factor (VEGF), and bone morphogenetic protein 2 (BMP-2) were evaluated in vitro with canine flexor tendon fibroblasts. The effects of single factors (PDGF-BB, bFGF, VEGF, or BMP-2) or a combination of factors (PDGF-BB and bFGF) on cell proliferation (ie, thymidine incorporation) and collagen production (ie, proline incorporation) were evaluated.
  
  
  RESULTS
  The results supported our hypotheses. Cell proliferation increased significantly with PDGF-BB and bFGF. Collagen production also increased significantly with PDGF-BB and bFGF. Cell proliferation and collagen production were unchanged with VEGF and BMP-2. A dose-response effect was seen for PDGF-BB combined with bFGF. The combination of PDGF-BB and bFGF led to an increase in cell proliferation but no change in collagen production compared with each factor alone.
  
  
  CONCLUSIONS
  The growth factors PDGF-BB and bFGF significantly increased flexor tendon fibroblast proliferation and matrix synthesis when applied singly. Administration of PDGF-BB and bFGF combined led to increased proliferation to single factors.
authors.affiliation: Department of Orthopaedic Research, Washington University, St. Louis, MO, USA. ThomopoulosS@msnotes.wustl.edu
authors.forename: Stavros
authors.initials: S
authors.lastname: Thomopoulos
authors.forename: Fred L
authors.initials: FL
authors.lastname: Harwood
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Silva
authors.forename: David
authors.initials: D
authors.lastname: Amiel
authors.forename: Richard H
authors.initials: RH
authors.lastname: Gelberman
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000378:metabolism*; D006133:Growth Substances / Q000494:pharmacology*; D023421:Models, Animal; D011392:Proline / Q000378:metabolism; D013710:Tendons / Q000378:metabolism*; D013936:Thymidine / Q000378:metabolism
chemical_list: D006133:Growth Substances; D003094:Collagen; D011392:Proline; D013936:Thymidine