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Home / Equine Research Bank / Cartilage / Effects of Dexamethasone Concentration and Timing of Exposur...
Cartilage2016; 7(1); 92-103; doi: 10.1177/1947603515595263

Effects of Dexamethasone Concentration and Timing of Exposure on Chondrogenesis of Equine Bone Marrow-Derived Mesenchymal Stem Cells.

Abstract: Dexamethasone is known to support mesenchymal stem cell (MSC) chondrogenesis, although the effects of dose and timing of exposure are not well understood. The objective of this study was to investigate these variables using a laboratory model of MSC chondrogenesis. Methods: Equine MSCs were encapsulated in agarose and cultured in chondrogenic medium with 1 or 100 nM dexamethasone, or without dexamethasone, for 15 days. Samples were analyzed for extracellular matrix (ECM) accumulation, prostaglandin E2 and alkaline phosphatase secretion, and gene expression of selected collagens and catabolic enzymes. Timing of exposure was evaluated by ECM accumulation after dexamethasone was withdrawn over the first 6 days, or withheld for up to 3 or 6 days of culture. Results: ECM accumulation was not significantly different between 1 and 100 nM dexamethasone, but was suppressed ~40% in dexamethasone-free cultures. Prostaglandin E2 secretion, and expression of catabolic enzymes, including matrix metalloproteinase 13, and type X collagen was generally lowest in 100 nM dexamethasone and not significantly different between 1 nM and dexamethasone-free cultures. Dexamethasone could be withheld for at least 2 days without affecting ECM accumulation, while withdrawal studies suggested that dexamethasone supports ECM accumulation beyond day 6. Conclusions: One nanomolar dexamethasone supported robust cartilage-like ECM accumulation despite not having an effect on markers of inflammation, although higher concentrations of dexamethasone may be necessary to suppress undesirable hypertrophic differentiation. While early exposure to dexamethasone was not critical, sustained exposure of at least a week appears to be necessary to maximize ECM accumulation.
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Publication Date: 2016-03-10 PubMed ID: 26958321PubMed Central: PMC4749745DOI: 10.1177/1947603515595263Google 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.

This research explores the impact of the concentration and exposure timing of Dexamethasone on the chondrogenesis process (the formation of cartilage) in horse bone marrow-derived mesenchymal stem cells. The findings suggest that while early exposure to the Dexamethasone is not vital, consistent exposure over a week or more appears to maximize cartilage-like matrix accumulation.

Objective and Method

  • The central objective of this research was to understand how variations in the dose and timing of exposure to Dexamethasone influence chondrogenesis in equine mesenchymal stem cells (MSCs).
  • Scientists created a laboratory model of MSC chondrogenesis where horse MSCs were encapsulated in agarose- a gel-forming substance, and then cultured in chondrogenic medium with 1 or 100 nM Dexamethasone, or without it, for 15 days.

Investigations and Results

  • The research focused on examining extracellular matrix (ECM) accumulation, prostaglandin E2 secretion, alkaline phosphatase secretion, and the gene expression of certain collagens and catabolic enzymes.
  • According to the findings, the accumulation of ECM was suppressed by about 40% in Dexamethasone-free cultures. On the other hand, it did not show a significant difference between 1 and 100 nM Dexamethasone.
  • The expression of matrix metalloproteinase 13, a kind of catabolic enzyme, and type X collagen, along with the secretion of prostaglandin E2, were generally lowest in 100 nM Dexamethasone. There was no significant difference between the 1 nM and dexamethasone-free cultures.
  • The researchers found that Dexamethasone could be withheld for at least 2 days without affecting ECM accumulation. On the other hand, stopping exposure to Dexamethasone after 6 days indicated that Dexamethasone supports ECM accumulation over a more extended period.

Conclusions

  • This research concluded that 1 nM Dexamethasone supported significant cartilage-like ECM accumulation, even without having an impact on inflammation markers.
  • Higher concentrations of Dexamethasone might be required to suppress unwanted hypertrophic differentiation – a process where cells change in response to various stimuli.
  • The study also suggested that early exposure to Dexamethasone is not critical. However, continued exposure for at least a week seems necessary to maximize ECM accumulation, thereby emphasizing the importance of dosage frequency in cell differentiation and cartilage formation.

Cite This Article

APA
Tangtrongsup S, Kisiday JD. (2016). Effects of Dexamethasone Concentration and Timing of Exposure on Chondrogenesis of Equine Bone Marrow-Derived Mesenchymal Stem Cells. Cartilage, 7(1), 92-103. https://doi.org/10.1177/1947603515595263

Publication

Cartilage
ISSN: 1947-6035
NlmUniqueID: 101518378
Country: United States
Language: English
Volume: 7
Issue: 1
Pages: 92-103

Researcher Affiliations

Tangtrongsup, Suwimol
  • Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
Kisiday, John D
  • Orthopaedic Research Center, Department of Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.

Conflict of Interest Statement

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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