title: Induction of Canonical Wnt Signaling by Synovial Overexpression of Selected Wnts Leads to Protease Activity and Early Osteoarthritis-Like Cartilage Damage.
abstract: Proteins from the Wnt signaling pathway are very important for joint development. Curiously, osteoarthritis (OA) is thought to be a recapitulation of developmental processes. Various members of the Wnt signaling pathway are overexpressed in the synovium during experimental OA. Here, we investigated the potency of specific Wnt proteins, when expressed in the synovium, to induce OA pathology. We overexpressed Wnt5a, Wnt8a, Wnt16, and WISP1 in the synovium using adenoviral vectors. We determined whether overexpression resulted in OA pathology by histology, and we measured whether Wnt signaling led to increased protease activity in the joint. Synovial overexpression of Wnt8a and Wnt16 led to canonical Wnt signaling in the cartilage, whereas overexpression of Wnt5a did not. Canonical Wnt signaling increased protease activity and induced cartilage damage shortly after overexpression. Specific blocking of the canonical Wnt signaling pathway with Dickkopf-1 reduced the Wnt-signaling-induced cartilage damage. By contrast, the noncanonical signaling Wnt5a did not cause cartilage lesions. Overexpression of WISP1, a downstream protein of canonical Wnt signaling, resulted in increased cartilage damage. In conclusion, our data show that canonical Wnts and WISP1, which we found overexpressed in the synovium during experimental OA, may conduce to OA pathology.
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Martijn H
authors.initials: MH
authors.lastname: van den Bosch
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands. Electronic address: arjen.blom@radboudumc.nl.
authors.forename: Arjen B
authors.initials: AB
authors.lastname: Blom
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Annet W
authors.initials: AW
authors.lastname: Sloetjes
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Marije I
authors.initials: MI
authors.lastname: Koenders
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Fons A
authors.initials: FA
authors.lastname: van de Loo
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Wim B
authors.initials: WB
authors.lastname: van den Berg
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Peter L
authors.initials: PL
authors.lastname: van Lent
authors.affiliation: Department of Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Peter M
authors.initials: PM
authors.lastname: van der Kraan
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental; D055511:CCN Intercellular Signaling Proteins / Q000378:metabolism*; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology*; D002460:Cell Line; D006801:Humans; D007717:Knee / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology*; D010447:Peptide Hydrolases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D013583:Synovial Membrane / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D060449:Wnt Signaling Pathway
chemical_list: D055511:CCN Intercellular Signaling Proteins; C492067:CCN4 protein, mouse; D011518:Proto-Oncogene Proteins; D051153:Wnt Proteins; D010447:Peptide Hydrolases