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Osmotic or Chemical Activation of the TRPV4 Ion Channel Enhances the Development of Chondrocyte-Based Tissue Engineered Cartilage

[+] Author Affiliations
Christopher J. O’Conor, Farshid Guilak

Duke University Medical Center, Durham, NCUniversity of North Carolina, Chapel Hill, NC

Halei C. Benefield

Duke University, Durham, NC

Wolfgang Liedtke

Duke University Medical Center, Durham, NC

Paper No. SBC2013-14042, pp. V01BT49A001; 2 pages
doi:10.1115/SBC2013-14042
From:
  • ASME 2013 Summer Bioengineering Conference
  • Volume 1B: Extremity; Fluid Mechanics; Gait; Growth, Remodeling, and Repair; Heart Valves; Injury Biomechanics; Mechanotransduction and Sub-Cellular Biophysics; MultiScale Biotransport; Muscle, Tendon and Ligament; Musculoskeletal Devices; Multiscale Mechanics; Thermal Medicine; Ocular Biomechanics; Pediatric Hemodynamics; Pericellular Phenomena; Tissue Mechanics; Biotransport Design and Devices; Spine; Stent Device Hemodynamics; Vascular Solid Mechanics; Student Paper and Design Competitions
  • Sunriver, Oregon, USA, June 26–29, 2013
  • Conference Sponsors: Bioengineering Division
  • ISBN: 978-0-7918-5561-4
  • Copyright © 2013 by ASME

abstract

Dynamic mechanical loading can enhance the formation of engineered cartilage, potentially through secondary biophysical effects such as changes in interstitial osmolarity. This study examined the effects of daily osmotic loading, as well as direct activation of the osmosensitive ion channel TRPV4, on the biochemical and functional properties of chondrocyte-laden cartilage constructs. Osmotic loading, as well as exposure to the TRPV4-specific agonist GSK1016790A, enhanced extracellular matrix (ECM) accumulation, and TRPV4 activation enhanced the functional properties of the constructs. This study implicates the Ca++-permeable TRPV4 ion channel in the metabolic response of articular chondrocytes to osmotic and mechanical loading. Furthermore, these results suggest that targeting TRPV4, either directly with channel agonists, or indirectly via osmotic loading, may provide a novel strategy for enhancing tissue engineered cartilage construct maturation.

Copyright © 2013 by ASME

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