Identification of the molecular response of articular cartilage to injury, by microarray screening

Francesco Dell'Accio, Cosimo De Bari, Noha A. Eltawil, Paul Vanhummelen, Costantino Pitzalis

Research output: Contribution to journalArticle

116 Citations (Scopus)

Abstract

Objective. To characterize the molecular response of adult human articular cartilage to acute mechanical injury.

Methods. An established ex vivo model was used to compare gene expression of adult human articular cartilage explants 24 hours after mechanical injury with that of uninjured controls by microarray analysis of gene expression. Confirmation for selected genes was obtained by real-time polymerase chain reaction and immunohistochemical analysis. Expression of selected genes was also investigated in preserved and osteoarthritic (OA) cartilage.

Results. Six hundred ninety genes were significantly regulated at least 2-fold following mechanical injury. They included genes previously reported to be differentially expressed in OA versus normal cartilage or having allelic variants genetically linked to OA. Significant functional clusters included genes associated with wound healing, developmental processes, and skeletal development. The transforming growth factor beta, fibroblast growth factor, and Wnt pathways were modulated. A systematic analysis of the Wnt signaling pathway revealed up-regulation of Wnt-16, down-regulation of FRZB, up-regulation of Wnt target genes, and nuclear localization of beta-catenin in injured cartilage. In addition, in OA, Wnt-16 and beta-catenin were barely detectable in preserved cartilage areas, but were dramatically up-regulated in areas of the same joint with moderate to severe OA damage.

Conclusion. Our findings indicate that mechanical injury to adult human articular cartilage results in the activation of a signaling response, with reactivation of morphogenetic pathways. Therapeutic targeting of such pathways may improve current protocols of joint surface defect repair and/or prevent the evolution of such lesions into posttramnatic OA.

Original languageEnglish
Pages (from-to)1410-1421
Number of pages12
JournalArthritis & Rheumatism
Volume58
Issue number5
Early online date25 Apr 2008
DOIs
Publication statusPublished - May 2008

Keywords

  • mesenchymal stem-cells
  • knee osteoarthritis
  • gene-expression
  • mechanical injury
  • thickness defects
  • TGF-beta
  • in-vivo
  • WNT
  • differentiation
  • chondrocyte

Cite this

Identification of the molecular response of articular cartilage to injury, by microarray screening. / Dell'Accio, Francesco; De Bari, Cosimo; Eltawil, Noha A.; Vanhummelen, Paul; Pitzalis, Costantino.

In: Arthritis & Rheumatism, Vol. 58, No. 5, 05.2008, p. 1410-1421.

Research output: Contribution to journalArticle

Dell'Accio, Francesco ; De Bari, Cosimo ; Eltawil, Noha A. ; Vanhummelen, Paul ; Pitzalis, Costantino. / Identification of the molecular response of articular cartilage to injury, by microarray screening. In: Arthritis & Rheumatism. 2008 ; Vol. 58, No. 5. pp. 1410-1421.
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