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

Cristóbal López-Jiménez; Loraine L.Y. Chiu; Stephen D. Waldman; Farshid Guilak; Thomas G. Koch

Osteoarthritis and Cartilage Open (Jun 2022)

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

Cristóbal López-Jiménez,
Loraine L.Y. Chiu,
Stephen D. Waldman,
Farshid Guilak,
Thomas G. Koch

Affiliations

Cristóbal López-Jiménez: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 22 College Ave W, Guelph, Ontario, N1G 1R7, Canada
Loraine L.Y. Chiu: 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
Stephen D. Waldman: 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
Farshid Guilak: 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
Thomas G. Koch: Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, 22 College Ave W, Guelph, Ontario, N1G 1R7, Canada; Corresponding author.

Journal volume & issue: Vol. 4, no. 2
p. 100263

Abstract

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Objective: To evaluate the effect of Transient Receptor Potential Vanilloid 4 (TRPV4) cation channel modulation on mesenchymal stromal cell (MSC)-derived neocartilage. Methods: 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). Results: GSK101 treatment (1 nM) increased ACAN levels after treatment for 1-h per day for 3 days. No increase was detected for hypertrophic markers RUNX2, MMP13, MMP1, ALP or COL10A1 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. Conclusions: 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.

Published in Osteoarthritis and Cartilage Open

ISSN: 2665-9131 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Medicine: Internal medicine: Specialties of internal medicine: Diseases of the musculoskeletal system
Website: https://www.journals.elsevier.com/osteoarthritis-and-cartilage-open/

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