title: In vitro model to study chondrogenic differentiation in tendinopathy.
abstract: BACKGROUND
  Treatment of midportion Achilles tendinopathy is hampered by limited knowledge of the pathophysiology.
  
  
  OBJECTIVE
  Chondrogenic differentiation of tendon cells might take place in midportion Achilles tendinopathy and could be used as a target for drug treatment. An in vitro model for chondrogenic differentiation would be useful to evaluate existing and future treatment opportunities.
  
  
  METHODS
  A controlled laboratory study.
  
  
  METHODS
  Perioperatively harvested tissue from human midportion Achilles tendinotic lesions and healthy Achilles tendons was analyzed by microscopy and real-time reverse transcription polymerase chain reaction. In vitro chondrogenic differentiation of tendon explants was induced using transforming-growth-factor beta. This model was modulated by removing the chondrogenic stimulus or adding triamcinolone or platelet-rich plasma.
  
  
  RESULTS
  Midportion Achilles tendinotic lesions had increased glycosaminoglycan staining and more rounded cell nuclei. Chondrogenic markers (sex-determining region Y)-box9, aggrecan, collagen 2, and RUNT-related transcription factor 2 were upregulated, but collagen 10 was not. Nondegenerative tendon explants cultured on chondrogenic medium had higher expression of aggrecan, collagen 2, and collagen 10 but not (sex-determining region Y)-box9 and RUNT-related transcription factor 2. Removing the chondrogenic stimulus decreased expression of aggrecan, collagen 2, and collagen 10. Both triamcinolone and platelet-rich plasma influenced the chondrogenic gene expression pattern in the in vitro model.
  
  
  CONCLUSIONS
  Chondrogenic differentiation is present in midportion Achilles tendinopathy. An in vitro model to study this chondrogenic differentiation was developed.
  
  
  CONCLUSIONS
  This model can be used to investigate chondrogenic differentiation as a possible target for drug treatment, contributing to the development of more successful mechanism-based treatment opportunities.
authors.affiliation: Erasmus MC, University Medical Center Rotterdam, Department of Orthopaedics, Room Ee1618, PO Box 1738, Rotterdam 3015 GE, The Netherlands. mariekedemos@hotmail.com
authors.forename: Marieke
authors.initials: M
authors.lastname: de Mos
authors.forename: Wendy
authors.initials: W
authors.lastname: Koevoet
authors.forename: Hans T M
authors.initials: HT
authors.lastname: van Schie
authors.forename: Nicole
authors.initials: N
authors.lastname: Kops
authors.forename: Holger
authors.initials: H
authors.lastname: Jahr
authors.forename: Jan A N
authors.initials: JA
authors.lastname: Verhaar
authors.forename: Gerjo J V M
authors.initials: GJ
authors.lastname: van Osch
mesh_terms: D000125:Achilles Tendon / Q000503:physiopathology; D000328:Adult; D000368:Aged; D001483:Base Sequence; D002454:Cell Differentiation / Q000235:genetics*; D019902:Chondrocytes / Q000166:cytology; D020219:Chondrogenesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D008957:Models, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D052256:Tendinopathy / Q000188:drug therapy / Q000503:physiopathology*; D020858:Tissue and Organ Harvesting; D016212:Transforming Growth Factor beta / Q000378:metabolism; D055815:Young Adult
chemical_list: D016212:Transforming Growth Factor beta