31-08-2016, 04:25 PM
Induction of Canonical Wnt Signaling by Synovial
Overexpression of Selected Wnts Leads to
Protease Activity and Early Osteoarthritis-Like Cartilage
Damage
1451892366-InductionofCanonicalWntSignalingbySynovial.pdf (Size: 3.72 MB / Downloads: 6)
The Wnt signaling pathway plays a central role in a plethora of
processes, including embryonic development, axis patterning,
cell proliferation, and cell migration. The development of the
articular joints, including cartilage, bone, and joints cavities, is
highly dependent on Wnt signaling.1e3 Osteoarthritis (OA) is
a degenerative joint disease with cartilage damage, synovial
inflammation, fibrosis, and osteophyte formation. OA probably
is in part the result of a recapitulation of developmental
processes in the joint, making Wnt signaling an alluring
pathway to study.4e6
In the past, we have found highly increased expression of
several Wnts specifically in the synovium of various murine
experimental OA models, as well as an increase in WNT1-
inducible signaling pathway protein 1 (WISP1), a downstream
protein of canonical Wnt signaling, in both the synovium and the cartilage. In addition, increased expression of WISP1 was
found in human OA cartilage.7
Wnt proteins are a family of lipid-modified glycoproteins
that can bind to Frizzled (Fzd) receptors. Wnt proteins
can signal via noncanonical and canonical signaling
pathways. Although the paradigm is shifting, Wnt5a is
historically considered to be a noncanonical protein,
whereas Wnt8a is considered a canonical Wnt protein. In
addition to WnteFzd interaction, binding to the coreceptor
complex of low-density lipoprotein receptor-related protein
(LRP) 5/6 is essential for b-cateninedependent canonical
signaling