In vitro model to study chondrogenic differentiation in tendinopathy

Am J Sports Med. 2009 Jun;37(6):1214-22. doi: 10.1177/0363546508331137. Epub 2009 Mar 11.


Background: Treatment of midportion Achilles tendinopathy is hampered by limited knowledge of the pathophysiology.

Hypothesis: 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.

Study: 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.

Conclusion: Chondrogenic differentiation is present in midportion Achilles tendinopathy. An in vitro model to study this chondrogenic differentiation was developed.

Clinical relevance: 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Achilles Tendon / physiopathology
  • Adult
  • Aged
  • Base Sequence
  • Cell Differentiation / genetics*
  • Chondrocytes / cytology
  • Chondrogenesis / genetics
  • Chondrogenesis / physiology*
  • Female
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Models, Genetic*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tendinopathy / drug therapy
  • Tendinopathy / physiopathology*
  • Tissue and Organ Harvesting
  • Transforming Growth Factor beta / metabolism
  • Young Adult


  • Transforming Growth Factor beta