Dr. Dell'Accio is a Clinician Scientist Fellow of the ARC.
Identification of the molecular response of articular cartilage to injury, by microarray screening: Wnt-16 expression and signaling after injury and in osteoarthritis
Article first published online: 25 APR 2008
Copyright © 2008 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 58, Issue 5, pages 1410–1421, May 2008
How to Cite
Dell'Accio, F., De Bari, C., Eltawil, N. M., Vanhummelen, P. and Pitzalis, C. (2008), Identification of the molecular response of articular cartilage to injury, by microarray screening: Wnt-16 expression and signaling after injury and in osteoarthritis. Arthritis & Rheumatism, 58: 1410–1421. doi: 10.1002/art.23444
- Issue published online: 25 APR 2008
- Article first published online: 25 APR 2008
- Manuscript Accepted: 1 FEB 2008
- Manuscript Received: 12 JUN 2007
- Arthritis Research Campaign (ARC). Grant Numbers: 16290, 17971
- MRC. Grant Number: G108/620
- Egyptian government
To characterize the molecular response of adult human articular cartilage to acute mechanical injury.
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.
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 β, 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 β-catenin in injured cartilage. In addition, in OA, Wnt-16 and β-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.
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 posttraumatic OA.