To seek shelter from the WNT in osteoarthritis? WNT-signaling as a target for osteoarthritis therapy.
Recent evidence from animal experiments and clinical samples points at a role for Wnt-signaling in osteoarthritis (OA) pathology. These pathways are key inducers and regulators of joint development, and are involved in formation of bone, cartilage and also synovium. Disregulation of members from this pathways have been described in OA. This makes the Wnt-family of proteins and signaling pathways an attractive target for therapy. Although knowledge is increasing rapidly it is still a challenge to decide on the best approach in targeting Wnt signaling. Activation of the canonical signaling pathway, which features intra-cellular accumulation of beta-catenin, is most often implicated in recent studies in OA pathology, in experimental OA and spondyloarthritis. However, direct targeting of beta-catenin is anticipated to be too hazardous, because of its importance for the maintenance of stability of articular chondrocyte phenotype and because of its proven role in carcinogenesis. A more attractive approach will be identifying the misexpression of specific Wnt-proteins or their inhibitors in various tissues that are important in OA, bone, cartilage and synovium, to point out targets for therapy. For example, recently it was shown that Wnt16 is strongly upregulated in cartilage after injury and in synovium in experimental OA, and the expression of this canonical Wnt may be responsible for OA-like changes. Alternatively, identifying more down stream Wnt signaling effector molecules, like WISP-1, for more specific therapy promises to be a safer and more efficient approach to find a treatment for this disease that heavily constrains millions of people each year.
Blom
Arjen B
AB
Experimental Rheumatology & Advanced Therapeutics, Radboud University Nijmegen Medical Centre Nijmegen, The Netherlands. a.blom@reuma.umcn.nl
van Lent
Peter L
PL
van der Kraan
Peter M
PM
van den Berg
Wim B
WB
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002356:Cartilage / Q000378:metabolism / Q000473:pathology; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008954:Models, Biological; D010003:Osteoarthritis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D051153:Wnt Proteins