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Home / Equine Research Bank / Osteoarthr Cartil Open / TRPV4 activation enhances compressive properties and glycosa...
Osteoarthritis and cartilage open2022; 4(2); 100263; doi: 10.1016/j.ocarto.2022.100263

TRPV4 activation enhances compressive properties and glycosaminoglycan deposition of equine neocartilage sheets.

Abstract: To evaluate the effect of Transient Receptor Potential Vanilloid 4 (TRPV4) cation channel modulation on mesenchymal stromal cell (MSC)-derived neocartilage. Unassigned: RT-PCR was performed to evaluate mRNA levels of chondrogenic, hypertrophic and candidate mechanoresponsive genes in equine neocartilage sheets exposed to pulses of the TRPV4 agonist (GSK101) at different concentrations (N ​= ​10). Biochemical assays and mechanical tests (double indentation and unconfined compression) evaluated neocartilage properties (N ​= ​5). Unassigned: GSK101 treatment (1 ​nM) increased levels after treatment for 1-h per day for 3 days. No increase was detected for hypertrophic markers , , , or at this concentration. This treatment regimen also increased sGAG content and enhanced compressive properties compared to untreated controls. GSK101 showed no effect on candidate mechanoresponsive genes at the time-point of analysis. Unassigned: Chemical activation of TRPV4 signalling can be used as a strategy to enhance matrix synthesis and maturation of MSC-derived engineered neocartilage and augment its load-bearing capacity.
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Publication Date: 2022-04-18 PubMed ID: 36475280PubMed Central: PMC9718125DOI: 10.1016/j.ocarto.2022.100263Google Scholar: Lookup
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  • Journal Article

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 investigates how activating Transient Receptor Potential Vanilloid 4 (TRPV4) improves both glycosaminoglycan (sGAG) deposition and compressive properties of mesenchymal stromal cell (MSC)-derived neocartilage, aiming to improve the maturation and load-bearing ability of artificially engineered neocartilage.

Research Purpose

  • The main aim of this research was to explore the effects of modulating the TRPV4 cation channel on MSC-derived neocartilage. The researchers hypothesized that the activation of this channel might enhance the functioning and development of engineered neocartilage.

Methodology

  • To gauge the impact of TRPV4 activation, the team exposed equine neocartilage sheets to varying concentrations of TRPV4 agonist (GSK101).
  • They then utilized RT-PCR to evaluate the mRNA levels of chondrogenic (related to cartilage production), hypertrophic (related to cell growth), and candidate mechanoresponsive genes.
  • Alongside this, they used biochemical assays and mechanical testing methods, like double indentation and unconfined compression, for analyzing the properties of the neocartilage.
  • Every experimental group consisted of five samples (N = 5 for neocartilage properties’ evaluation, and N = 10 for gene expression evaluation).

Findings and Conclusions

  • The analysis revealed that a specific regimen of GSK101 treatment (1 nM for 1 hour per day for 3 days) led to an increase in chondrogenic gene expression, but didn’t affect hypertrophic markers.
  • Moreover, this treatment approach also resulted in a significant increase in the sGAG content. sGAGs are important components of the cartilage extracellular matrix and play a critical role in maintaining the structural integrity of the cartilage.
  • Simultaneously, the compressive properties of the neocartilage, signifying the ability to bear loads, were also enhanced. This finding suggests that the activation of TRPV4 signaling contributes to the maturation and mechanical functionality of neocartilage.
  • The study concluded that chemical activation of TRPV4 signaling could serve as a promising strategy for enhancing matrix synthesis in engineered neocartilage, and increase its load-bearing capacity; hence, possibly improving the therapeutic efficiency of MSC-derived engineered cartilage.

Cite This Article

APA
López-Jiménez C, Chiu LLY, Waldman SD, Guilak F, Koch TG. (2022). TRPV4 activation enhances compressive properties and glycosaminoglycan deposition of equine neocartilage sheets. Osteoarthr Cartil Open, 4(2), 100263. https://doi.org/10.1016/j.ocarto.2022.100263

Publication

Osteoarthritis and cartilage open
ISSN: 2665-9131
NlmUniqueID: 101767068
Country: England
Language: English
Volume: 4
Issue: 2
Pages: 100263
PII: 100263

Researcher Affiliations

López-Jiménez, Cristóbal
  • Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 22 College Ave W, Guelph, Ontario, N1G 1R7, Canada.
Chiu, Loraine L Y
  • Li Ka Shing Knowledge Institute, St Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1T8, Canada.
  • Department of Chemical Engineering, Ryerson University, 350 Victoria Street, Toronto, Ontario, M5B 2K3, Canada.
Waldman, Stephen D
  • Li Ka Shing Knowledge Institute, St Michael's Hospital, 30 Bond Street, Toronto, Ontario, M5B 1T8, Canada.
  • Department of Chemical Engineering, Ryerson University, 350 Victoria Street, Toronto, Ontario, M5B 2K3, Canada.
Guilak, Farshid
  • Department of Orthopaedic Surgery, Washington University, St. Louis, MO, USA, 63110.
  • Shriners Hospitals for Children - St. Louis, St. Louis, MO, USA, 63110.
  • Center of Regenerative Medicine, Washington University, St. Louis, MO, USA, 63110.
Koch, Thomas G
  • Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 22 College Ave W, Guelph, Ontario, N1G 1R7, Canada.

Conflict of Interest Statement

Thomas Koch is the founder, CEO and CSO of eQcell Inc, ON, Canada. Farshid Guilak is a shareholder and employee of Cytex Therapeutics, Inc. The remaining authors declare no potential conflict of interests with respect to the research, authorship, and/or publication of this article.

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Citations

This article has been cited 1 times.
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