Study identifies molecular response of cartilage...(ulation of the ligand Wnt-16 down-regula...),Health

Date:5/8/2008

ulation of the ligand Wnt-16, down-regulation of the secreted inhibitor FRZB, nuclear accumulation of -catenin, and upregulation of several known WNT target genes supporting net activation of this signalling pathway. Wnt-16 and -catenin were barely detectable in preserved cartilage from OA joints but dramatically up-regulated in areas of the same joint with moderate to severe OA damage.

This study indicates that several genes encoding signalling molecules are regulated following cartilage injury in adult individuals. Although it is tempting to speculate that some of these genes represent a reparative response, Dr DellAccio stresses that at the moment we do not know whether such phenomena are supporting repair (hence representing potential therapeutic tools) or even play a role in the progression of damage (hence potential therapeutic targets). Hence further investigation is needed to optimally target the respective pathways to promote joint surface cartilage defect repair or to stop further joint surface breakdown, thereby preventing the development of posttraumatic OA.

In a related editorial, Dr. Tonia L. Vincent and Dr. Jeremy Saklatva of Imperial College London raise the question of whether the response of cartilage to injury is relevant to osteoarthritis. As they argue, the findings of Dr. DellAccio and his colleagues suggest that Wnt activity may be important in OA, possibly driving bone changes in disease, such as osteophyte formation, but not necessarily directly injury-regulated. Yet, as they also note, studies devoted to unraveling the link between joint injury and OA risk are leading the way toward a better understanding of the tissue processes and the signaling pathways activated in disease. Further investigation into the pathways revealed in this injury microarray is likely to be highly informative, Dr. Vincent states.

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Contact: Sean Wagner swagner@wiley.com 781-388-8550 Wiley-Blackwell Source:Eurekalert

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