In vitro model to study chondrogenic differentiation in tendinopathy
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.
|Keywords||Achilles tendinopathy, chondrogenic differentiation, in vitro model, platelet-rich plasma (PRP), triamcinolone|
|Sponsor||In 2009: Erasmus MC, Department of Orthopaedics, University Medical Centre Rotterdam|
|Persistent URL||dx.doi.org/10.1177/0363546508331137, hdl.handle.net/1765/16118|
|Note||Epub 2009 Mar 11.|
de Mos, M., Koevoet, J.L.M., van Schie, J.T.M., Kops, N., Jahr, H., Verhaar, J.A.N., & van Osch, G.J.V.M.. (2009). In vitro model to study chondrogenic differentiation in tendinopathy. American Journal of Sports Medicine, 37(6), 1214–1222. doi:10.1177/0363546508331137