Enhancement of Runx2 expression is potentially linked to β-catenin accumulation in canine intervertebral disc degeneration

J Cell Physiol. 2015 Jan;230(1):180-90. doi: 10.1002/jcp.24697.


Intervertebral disc degeneration (IVDD) greatly affects the quality of life. The nucleus pulposus (NP) of chondrodystrophic dog breeds (CDBs) is similar to the human NP because the cells disappear with age and are replaced by fibrochondrocyte-like cells. Because IVDD develops as early as within the first year of life, we used canines as a model to investigate the in vitro mechanisms underlying IVDD. The mechanism underlying age-related IVDD, however, is poorly understood. Several research groups have suggested that Wnt/β-catenin signaling plays an important role in IVDD. However, the role of Wnt/β-catenin signals in IVD cells is not yet well understood. Here, we demonstrate that Wnt/β-catenin signaling could enhance Runx2 expression in IVDD and lead to IVD calcification. Nucleus pulposus (NP) tissue was obtained from Beagle dogs after evaluation of the degeneration based on magnetic resonance imaging (MRI). Histological analysis showed that lack of Safranin-O staining, calcified area, and matrix metalloproteinase (MMP) 13-positive cells increased with progression of the degeneration. Furthermore, the levels of β-catenin- and Runx2-positive cells also increased. Real-time reverse-transcription polymerase chain reaction analysis showed that the MRI signal intensity and mRNA expression levels of β-catenin and Runx2 are correlated in NP tissues. Moreover, supplementation of LiCl induced β-catenin accumulation and Runx2 expression. In contrast, FH535 inhibited LiCl-induced upregulation. These results suggest that Runx2 transcript and protein expression, potentially in combination with β-catenin accumulation, are enhanced in degenerated and calcified intervertebral discs of CDBs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcinosis / pathology*
  • Cells, Cultured
  • Core Binding Factor Alpha 1 Subunit / biosynthesis*
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Dogs
  • Extracellular Matrix Proteins / biosynthesis
  • Gene Expression
  • Intervertebral Disc / pathology*
  • Intervertebral Disc Degeneration / pathology*
  • Lithium Chloride / pharmacology
  • Male
  • Matrix Metalloproteinase 13 / metabolism
  • RNA, Messenger / biosynthesis
  • Sulfonamides / pharmacology
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway
  • beta Catenin / genetics
  • beta Catenin / metabolism*


  • Core Binding Factor Alpha 1 Subunit
  • Extracellular Matrix Proteins
  • FH535
  • RNA, Messenger
  • Sulfonamides
  • Wnt Proteins
  • beta Catenin
  • Matrix Metalloproteinase 13
  • Lithium Chloride