Premium
Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration
Author(s) -
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.
Publication year - 2012
Publication title -
journal of orthopaedic research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.041
H-Index - 155
eISSN - 1554-527X
pISSN - 0736-0266
DOI - 10.1002/jor.22000
Subject(s) - wnt signaling pathway , degeneration (medical) , downregulation and upregulation , microbiology and biotechnology , cell , signal transduction , chemistry , medicine , biology , pathology , biochemistry , gene
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