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Journal of equine science2014; 25(1); 7-13; doi: 10.1294/jes.25.7

Regulation of Tenomodulin Expression Via Wnt/β-catenin Signaling in Equine Bone Marrow-derived Mesenchymal Stem Cells.

Abstract: Tenomodulin has been recognized as a biomarker for tendon differentiation, and its gene expression is regulated by several transcription factors including Scleraxis and Mohawk. In this study, we found a novel regulatory mechanism of tenomodulin expression. Equine bone marrow-derived mesenchymal stem cells (BMSCs) in monolayer culture showed a low mRNA level of tenomodulin in comparison with the level in the tendon. When cultured in collagen gel containing a glycogen synthase kinase-3 (GSK-3) inhibitor (BIO), expression of tenomodulin in BMSCs increased up to the level in the tendon. Participation of GSK-3 in its gene expression was further demonstrated by a gene silencing experiment with small interference RNA corresponding to GSK-3, suggesting that Wnt/β-catenin signaling mediated expression of tenomodulin. These results were confirmed by nuclear translocation of β-catenin in BIO-treated BMSCs cultured in collagen gel. Under this culture condition, expression of tenomodulin-related transcription factors including Scleraxis and Mohawk was not affected, suggesting that Wnt/β-catenin signaling was independent from these transcription factors. Additionally, BIO strongly enhanced expression of type XIV collagen in collagen-embedded BMSCs up to the level in the tendon, and other tendon-related extracellular matrix components such as decorin and fibromodulin were also upregulated. Taken together, these results indicated that activation of Wnt/β-catenin signaling could induce differentiation of BMSCs into tenomodulin-expressing tendon cells in collagen gel.
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Publication Date: 2014-04-22 PubMed ID: 24834008PubMed Central: PMC4019198DOI: 10.1294/jes.25.7Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article explores how the Wnt/β-catenin signaling pathway regulates the expression of tenomodulin, a biomarker for tendon differentiation, in equine bone marrow-derived mesenchymal stem cells (BMSCs). The findings propose a new mechanism by which BMSCs could be differentiated into tenomodulin-expressing cells.

Background and Aims

  • The authors of the study aimed to understand the mechanisms controlling the expression of tenomodulin, a well-known biomarker that indicates the differentiation of cells into tendon tissue.
  • The primary concern of the researchers was to verify whether the Wnt/β-catenin signaling pathway was involved in the regulation of tenomodulin in equine bone marrow-derived mesenchymal stem cells.

Methodology

  • BMSCs were cultured in a collagen gel containing a glycogen synthase kinase-3 (GSK-3) inhibitor (BIO). Subsequent examination showed increased tenomodulin expression.
  • Experiments using small interfering RNA to silence GSK-3 gene activity demonstrated the connection between GSK-3 and tenomodulin expression.
  • Confirmation of this mechanism was made through the observation of β-catenin nuclear translocation in the treated BMSCs, indicating engagement of the Wnt/β-catenin pathway.
  • Following the experiments, the relationship between Wnt/β-catenin signaling and other known tenomodulin-regulating transcription factors, such as Scleraxis and Mohawk, was examined. However, these factors did not seem to have an impact subsequent to the activation of Wnt/β-catenin signaling.

Findings

  • BIO treatment stimulated a significant increase in the expression of tenomodulin in the treated BMSCs to a level typical within tendons. This includes the overexpression of other tendon-associated extracellular matrix components like type XIV collagen, decorin, and fibromodulin.
  • The study evidenced Wnt/β-catenin signaling as a critical component in the regulation of tenomodulin expression, independent of other transcription factors usually associated with tenomodulin regulation.
  • In conclusion, activating the Wnt/β-catenin pathway can potentially guide the differentiation of stem cells into tenomodulin-expressing tendon cells.

Cite This Article

APA
Miyabara S, Yuda Y, Kasashima Y, Kuwano A, Arai K. (2014). Regulation of Tenomodulin Expression Via Wnt/β-catenin Signaling in Equine Bone Marrow-derived Mesenchymal Stem Cells. J Equine Sci, 25(1), 7-13. https://doi.org/10.1294/jes.25.7

Publication

Journal of equine science
ISSN: 1340-3516
NlmUniqueID: 9503751
Country: Japan
Language: English
Volume: 25
Issue: 1
Pages: 7-13

Researcher Affiliations

Miyabara, Shihori
  • Department of Tissue Physiology, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Yuda, Yohei
  • Department of Tissue Physiology, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.
Kasashima, Yoshinori
  • Laboratory of Clinical Science and Pathobiology, Equine Research Institute, Japan Racing Association, Tochigi 320-8056, Japan.
Kuwano, Atsutoshi
  • Laboratory of Clinical Science and Pathobiology, Equine Research Institute, Japan Racing Association, Tochigi 320-8056, Japan.
Arai, Katsuhiko
  • Department of Tissue Physiology, Tokyo University of Agriculture and Technology, Tokyo 183-8509, Japan.

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Citations

This article has been cited 20 times.
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