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- Title
Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration.
- Authors
Smolders, Lucas A.; Meij, Björn P.; Riemers, Frank M.; Licht, Ruud; Wubbolts, Richard; Heuvel, Douwe; Grinwis, Guy C.M.; Vernooij, Hans C.M.; Hazewinkel, Herman A.W.; Penning, Louis C.; Tryfonidou, Marianna A.
- Abstract
The notochordal cell (NC) of the nucleus pulposus (NP) is considered a potential NP progenitor cell, and early intervertebral disk (IVD) degeneration involves replacement of NCs by chondrocyte-like cells (CLCs). Wnt/β-catenin signaling plays a crucial role in maintaining the notochordal fate during embryogenesis, but is also involved in tissue degeneration and regeneration. The canine species, which can be subdivided into non-chondrodystrophic and chondrodystrophic breeds, is characterized by differential maintenance of the NC: in non-chondrodystrophic dogs, the NC remains the predominant cell type during the majority of life, with IVD degeneration only occurring at old age; conversely, in chondrodystrophic dogs the NC is lost early in life, with concurrent degeneration of all IVDs. This study investigated Wnt/β-catenin signaling in the healthy, NC-rich NP and early degenerated, CLC-rich NP of both breed types by immunohistochemistry of β-catenin and relative gene expression of brachyury and cytokeratin 8 (notochordal markers) and Wnt targets axin2, cyclin D1, and c-myc. Both NCs and CLCs showed nuclear and cytoplasmic β-catenin protein expression and axin2 gene expression, but β-catenin signal intensity and Wnt target gene expression were higher in the CLC-rich NP. Primary NCs in monolayer culture (normoxic conditions) showed Wnt/β-catenin signaling comparable to the in vivo situation, with increased cyclin D1 and c-myc gene expression. In conclusion, Wnt/β-catenin signaling activity in the NC within the NC-rich NP and in culture supports the role of this cell as a potential progenitor cell; increased Wnt/β-catenin signaling activity in early IVD degeneration may be a reflection of its dual role. © 2011 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:950-957, 2012
- Subjects
NOTOCHORD; INTERVERTEBRAL disk diseases; CATENINS; DOG anatomy; DOG diseases
- Publication
Journal of Orthopaedic Research, 2012, Vol 30, Issue 6, p950
- ISSN
0736-0266
- Publication type
Article
- DOI
10.1002/jor.22000