Calcineurin Inhibitors Promote Chondrogenic Marker Expression of Dedifferentiated Human Adult Chondrocytes via Stimulation of Endogenous TGF beta 1 Production

Anna Windt, Holger Jahr, Eric Farrell, Jan Verhaar, HH Weinans, Gerjo van Osch

Research output: Contribution to journalArticleAcademicpeer-review

22 Citations (Scopus)

Abstract

In vitro chondrocyte expansion is required for several cell-based approaches for the repair of chondral lesions. During expansion, loss of chondrogenic phenotype takes place (dedifferentiation). The objective of this study was to investigate calcineurin (Cn) as a potential target to improve chondrocyte phenotype for cartilage repair purposes. Cn activity in human articular chondrocytes was significantly increased during dedifferentiation and decreased during redifferentiation in vitro. Inhibition of Cn activity by FK506 increased the expression of chondrogenic markers collagen type 2, aggrecan, and SOX9 in culture-expanded cells. Addition of FK506 increased endogenous transforming growth factor (TGF) beta 1 expression on both mRNA and protein level. The effect of FK506 on chondrogenic markers was abolished by addition of anti-TGF beta 1 antibody, indicating that the endogenous TGF beta 1 was necessary to increase chondrogenic marker expression. We also showed that chondrocyte redifferentiation by TGF beta requires calcium influx and does not depend on changes in Cn activity. In conclusion, inhibition of Cn activity by FK506 increases the expression of chondrogenic markers via endogenous TGF beta 1 production in human articular chondrocytes. Cn inhibitors might be an alternative for the application of (recombinant) TGF beta, to promote chondrocyte phenotype for cell-based cartilage repair procedures.
Original languageUndefined/Unknown
Pages (from-to)1-10
Number of pages10
JournalTissue Engineering Part A
Volume16
Issue number1
DOIs
Publication statusPublished - 2010

Research programs

  • EMC MM-01-51-01
  • EMC OR-01-62-02

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