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Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration.
J Orthop Res 2012; 30(6):950-7JO

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.

Authors+Show Affiliations

Department of Clinical Sciences of Companion Animals, Utrecht University, Yalelaan 108, 3508 TD, Utrecht, The Netherlands. l.a.smolders@uu.nlNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

22083942

Citation

Smolders, Lucas A., et al. "Canonical Wnt Signaling in the Notochordal Cell Is Upregulated in Early Intervertebral Disk Degeneration." Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, vol. 30, no. 6, 2012, pp. 950-7.
Smolders LA, Meij BP, Riemers FM, et al. Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration. J Orthop Res. 2012;30(6):950-7.
Smolders, L. A., Meij, B. P., Riemers, F. M., Licht, R., Wubbolts, R., Heuvel, D., ... Tryfonidou, M. A. (2012). Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration. Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society, 30(6), pp. 950-7. doi:10.1002/jor.22000.
Smolders LA, et al. Canonical Wnt Signaling in the Notochordal Cell Is Upregulated in Early Intervertebral Disk Degeneration. J Orthop Res. 2012;30(6):950-7. PubMed PMID: 22083942.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Canonical Wnt signaling in the notochordal cell is upregulated in early intervertebral disk degeneration. AU - Smolders,Lucas A, AU - Meij,Björn P, AU - Riemers,Frank M, AU - Licht,Ruud, AU - Wubbolts,Richard, AU - Heuvel,Douwe, AU - Grinwis,Guy C M, AU - Vernooij,Hans C M, AU - Hazewinkel,Herman A W, AU - Penning,Louis C, AU - Tryfonidou,Marianna A, Y1 - 2011/11/14/ PY - 2011/03/10/received PY - 2011/10/13/accepted PY - 2011/11/16/entrez PY - 2011/11/16/pubmed PY - 2012/5/23/medline SP - 950 EP - 7 JF - Journal of orthopaedic research : official publication of the Orthopaedic Research Society JO - J. Orthop. Res. VL - 30 IS - 6 N2 - 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. SN - 1554-527X UR - https://www.unboundmedicine.com/medline/citation/22083942/Canonical_Wnt_signaling_in_the_notochordal_cell_is_upregulated_in_early_intervertebral_disk_degeneration_ L2 - https://doi.org/10.1002/jor.22000 DB - PRIME DP - Unbound Medicine ER -