Dell'Accio F et al. – 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. Methods
Study to characterize the molecular response of adult human articular cartilage to acute mechanical injury
Gene expression of adult human articular cartilage explants 24 h after mechanical injury was compared with that of uninjured controls by microarray analysis of gene expression
Confirmation for selected genes was obtained by RT-PCR and IHC analysis
Expression of selected genes was also investigated in preserved and OA cartilage
Results
690 genes were significantly regulated at least 2-fold following mechanical injury
They included genes previously reported to be differentially expressed in OA vs 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 TGFβ, FGF, and Wnt pathways were modulated
Up-regulation of Wnt-16, down-regulation of FRZB, up-regulation of Wnt target genes, and nuclear localization of β-catenin in injured cartilage was noted
In addition, in OA, Wnt-16 and β-catenin were barely detectable in preserved cartilage areas
However, they were dramatically up-regulated in areas of the same joint with moderate to severe OA damage
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