Evaluation of the association between runt-related transcription factor 2 expression and intervertebral disk aging in dogs

Itoh, Hisanori; Hara, Yasushi; Tagawa, Masahiro; Kato, Tsuyoshi; Ochi, Hiroki; Koga, Daisuke; Okawa, Atsushi; Asou, Yoshinori

doi:10.2460/ajvr.73.10.1553

Cited by 7 publications

(8 citation statements)

References 32 publications

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“…In addition, Runx2 may also be implicated in the progression of intervertebral disc aging and calcification in humans and CDBs, and this induction occurs prior to MMP‐13 expression (Rutges et al, ; Itoh et al, ), indicating that Runx2 plays an important role in IVD degeneration.…”

Section: Discussionmentioning

confidence: 99%

“…To measure and normalize the MRI signal intensity of NP tissue, we determined the disc center‐to‐cerebrospinal fluid (DC:CSF) T2‐weighted signal intensity ratio, which was reported previously by Itoh et al (). For DC:CSF determination, the plane with the subjectively brightest discs on midsagittal T2‐weighted images was chosen, and regions of interest were selected centrally in the high‐signal area of each disc and in the free CSF region.…”

Section: Methodsmentioning

confidence: 99%

“…Another important factor in the process of disc degeneration is Runt‐related transcription factor 2 (Runx2) expression. A previous report suggested that Runx2 is also implicated in the progression of intervertebral disc aging and calcification in humans and CDBs (Rutges et al, ; Itoh et al, ).…”

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confidence: 99%

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Enhancement of Runx2 Expression Is Potentially Linked to β‐Catenin Accumulation in Canine Intervertebral Disc Degeneration

Iwata

Aikawa

Hakozaki

et al. 2014

Journal Cellular Physiology

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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.

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Enhancement of Runx2 Expression Is Potentially Linked to β‐Catenin Accumulation in Canine Intervertebral Disc Degeneration

Iwata

Aikawa

Hakozaki

et al. 2014

Journal Cellular Physiology

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“…Although some studies have documented the BMP-induced stimulation of chondrogenesis and the regeneration of the extracellular matrix of the intervertebral disc (8,9), another study demonstrated no effect of BMPs in preventing the degeneration of the intervertebral disc, but demonsrated that it led to intervertebral disc calcification (10). The expression of runt-related transcription factor 2 (Runx2), a key transcription factor for chondrocyte hypertrophic differentiation (11), has been shown to be upregulated in the degenerative discs of dogs (12) and humans (13). Unlike dystrophic calcification, disc ossification is a positive osteogenic process associated with osteoblasts (14); however, the origin of osteogenic cells remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Sequencing and bioinformatics analysis of the differentially expressed genes in herniated discs with or without calcification

Shao

Jiang

et al. 2016

International Journal of Molecular Medicine

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The purpose of this study was to detect the differentially expressed genes between ossified herniated discs and herniated discs without ossification. In addition, we sought to identify a few candidate genes and pathways by using bioinformatics analysis. We analyzed 6 samples each of ossified herniated discs (experimental group) and herniated discs without ossification (control group). Purified mRNA and cDNA extracted from the samples were subjected to sequencing. The NOISeq method was used to statistically identify the differentially expressed genes (DEGs) between the 2 groups. An in-depth analysis using bioinformatics tools based on the DEGs was performed using Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction network analysis. The top 6 DEGs were verified using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 132 DEGs was detected. A total of 129 genes in the ossified group were upregulated and 3 genes were found to be downregulated as compared to the control group. The top 3 cellular components in GO ontologies analysis were extracellular matrix components. GO functions were mainly related to the glycoprotein in the cell membrane and extracellular matrix. The GO process was related to completing response to stimulus, immune reflex and defense. The top 5 KEGG enrichment pathways were associated with infection and inflammation. Three of the top 20 DEGs [sclerostin (SOST), WNT inhibitory factor 1 (WIF1) and secreted frizzled related protein 4 (SFRP4)] were related to the inhibition of the Wnt pathway. The ossified discs exhibited a higher expression of the top 6 DEGs [SOST, joining chain of multimeric IgA and IgM (IGJ; also known as JCHAIN), defensin alpha 4 (DEFA4), SFRP4, proteinase 3 (PRTN3) and cathepsin G (CTSG)], with the associated P-values of 0.045, 0.000, 0.008, 0.010, 0.015 and 0.002, respectively, as calculated by the independent sample t-test. The gene expression profiling of the 2 groups revealed differential gene expression. Thus, our data suggest that Wnt pathway abnormality and local inflammation may be related to disc ossification.

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“…The adoptive scoring system was that described by Itoh et al [ 11 ]; cell counts were performed by 2 independent observers. More than 100 cells in each sample were examined to evaluate the proportion of cells that showed a positive reaction for NG2 proteoglycan.…”

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confidence: 99%

Expression of NG2 proteoglycan in the degenerated intervertebral disc in dachshunds

Abdelhakiem

Yamashita

Atiba

et al. 2016

The Journal of Veterinary Medical Science

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The pathogenesis of intervertebral disc (IVD) degeneration is not fully understood. The biomolecular signaling pathways involved in the IVD degeneration require further investigation. The aim of this study was to investigate the expression of NG2 proteoglycan in the degenerated IVD. IVD samples were obtained from 16 Dachshunds that were confirmed to have IVD herniation and subsequently underwent hemilaminectomy. The samples were subjected to histological and immunohistochemical (IHC) examinations. IHC revealed positive results for the expression of NG2 proteoglycan in all examined samples. The results showed the expression of NG2 proteoglycan by the degenerated IVDs.

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Evaluation of the association between runt-related transcription factor 2 expression and intervertebral disk aging in dogs

Abstract: Results indicated that RUNX2 mRNA and protein expression in the NP are enhanced in aging intervertebral disks in dogs.

Cited by 7 publications

References 32 publications

Enhancement of Runx2 Expression Is Potentially Linked to β‐Catenin Accumulation in Canine Intervertebral Disc Degeneration

Enhancement of Runx2 Expression Is Potentially Linked to β‐Catenin Accumulation in Canine Intervertebral Disc Degeneration

Sequencing and bioinformatics analysis of the differentially expressed genes in herniated discs with or without calcification

Expression of NG2 proteoglycan in the degenerated intervertebral disc in dachshunds

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