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Journal of equine science2022; 33(2); 19-26; doi: 10.1294/jes.33.19

The combination of BMP12 and KY02111 enhances tendon differentiation in bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs).

Abstract: The Wingless and Int-1 (WNT) and bone morphogenic protein/growth differentiation factor (BMP/GDF) signalling pathways contribute significantly to the development of the musculoskeletal system. The mechanism by which they contribute is as follows: BMP/GDF signalling usually promotes tendon differentiation, whereas WNT signalling inhibits it. We hypothesised that inhibiting WNT and subsequently stimulating BMP signalling may enhance the tenogenic differentiation of stem cells. The objective of this study was to determine whether a combination of WNT inhibitor (KY02111) and BMP12/GDF7 protein could enhance the differentiation of bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs) into tenocytes. Cells were cultured in five treatments: control, BMP12, and three different combinations of BMP12 and KY02111. The results indicated that a 1-day treatment with KY02111 followed by a 13-day treatment with BMP12 resulted in the highest tenogenic differentiation score in this experiment. The effect of KY02111 is dependent on the incubation time, with 1 day being better than 3 or 5 days. This combination increased tenogenic gene marker expression, including SCX, TNMD, DCN, and TNC, as well as COL1 protein expression. In conclusion, we propose that a combination of BMP12 and KY02111 can enhance the in vitro tenogenic differentiation of BM-eMSCs more than BMP12 alone. The findings of this study might be useful for improving tendon differentiation protocols for stem cell transplantation and application to tendon regeneration.
Publication Date: 2022-07-06 PubMed ID: 35847484PubMed Central: PMC9260033DOI: 10.1294/jes.33.19Google Scholar: Lookup
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  • Journal Article

Summary

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The research examines the interaction of bone morphogenic protein 12 (BMP12) and Wingless and Int-1 inhibitor (KY02111) on equine stem cells, concluding that their combined use enhances the cells’ ability to differentiate into tendon cells.

Research Objectives

The objectives of the research involved investigation of the interaction between of BMP12 and KY02111 towards the differentiation of bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs) into tenocytes, or tendon cells. The hypothesis was that suppressing the WNT pathway (using WNT inhibitor KY02111) and stimulating the BMP signalling would promote this differentiation.

Methodology

  • Equine stem cells were subjected to five different treatments: a control group, BMP12 alone, and three combinations of BMP12 and KY02111.
  • Within the combination groups, the treatment varied based on the length of exposure to KY02111 (WNT inhibitor) followed by BMP12.
  • The researchers analyzed the tenogenic differentiation (transformation into tendon cells), looking particularly at gene markers such as SCX, TNMD, DCN, TNC, and COL1 protein expression.

Findings

  • The results revealed that a one-day exposure to KY02111 followed by a 13-day exposure to BMP12 led to the highest rates of tenogenic differentiation. Longer occurrences of exposure to KY02111 (3 or 5 days) were found to be less effective.
  • The researchers noticed an increase in tenogenic gene marker expression, implying a tendency toward tendon cell formation in the groups that were exposed to KY02111 before BMP12.

Conclusion

  • The study found that the combined use of BMP12 and KY02111 had more potential in fostering the differentiation of equine stem cells into tendon cells compared to using BMP12 alone.
  • As a result, the research suggested that these findings could be important for developing improved methods for tendon regeneration utilizing stem cell transplantation, particularly in medical and veterinary practices.

Cite This Article

APA
Supokawej A, Korchunjit W, Wongtawan T. (2022). The combination of BMP12 and KY02111 enhances tendon differentiation in bone marrow-derived equine mesenchymal stromal cells (BM-eMSCs). J Equine Sci, 33(2), 19-26. https://doi.org/10.1294/jes.33.19

Publication

ISSN: 1340-3516
NlmUniqueID: 9503751
Country: Japan
Language: English
Volume: 33
Issue: 2
Pages: 19-26

Researcher Affiliations

Supokawej, Aungkura
  • Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand.
Korchunjit, Wasamon
  • Department of Clinical Microscopy, Faculty of Medical Technology, Mahidol University, Nakhon Pathom 73170, Thailand.
  • Laboratory of Cellular Biomedicine, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand.
Wongtawan, Tuempong
  • Akkhararatchakumari Veterinary College, Walailak University, Nakhon Si Thammarat 80160, Thailand.
  • Centre for One Health, Walailak University, Nakhon Si Thammarat 80160, Thailand.
  • Laboratory of Cellular Biomedicine, Faculty of Veterinary Science, Mahidol University, Nakhon Pathom 73170, Thailand.

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Citations

This article has been cited 1 times.
  1. Jiang L, Lu J, Chen Y, Lyu K, Long L, Wang X, Liu T, Li S. Mesenchymal stem cells: An efficient cell therapy for tendon repair (Review).. Int J Mol Med 2023 Aug;52(2).
    doi: 10.3892/ijmm.2023.5273pubmed: 37387410google scholar: lookup