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Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis.

Publication ,  Journal Article
O'Conor, CJ; Ramalingam, S; Zelenski, NA; Benefield, HC; Rigo, I; Little, D; Wu, C-L; Chen, D; Liedtke, W; McNulty, AL; Guilak, F
Published in: Sci Rep
July 8, 2016

Osteoarthritis (OA) is a progressive degenerative disease of articular cartilage and surrounding tissues, and is associated with both advanced age and joint injury. Biomechanical factors play a critical role in the onset and progression of OA, yet the mechanisms through which physiologic or pathologic mechanical signals are transduced into a cellular response are not well understood. Defining the role of mechanosensory pathways in cartilage during OA pathogenesis may yield novel strategies or targets for the treatment of OA. The transient receptor potential vanilloid 4 (TRPV4) ion channel transduces mechanical loading of articular cartilage via the generation of intracellular calcium ion transients. Using tissue-specific, inducible Trpv4 gene-targeted mice, we demonstrate that loss of TRPV4-mediated cartilage mechanotransduction in adulthood reduces the severity of aging-associated OA. However, loss of chondrocyte TRPV4 did not prevent OA development following destabilization of the medial meniscus (DMM). These results highlight potentially distinct roles of TRPV4-mediated cartilage mechanotransduction in age-related and post-traumatic OA, and point to a novel disease-modifying strategy to therapeutically target the TRPV4-mediated mechanotransduction pathway for the treatment of aging-associated OA.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

July 8, 2016

Volume

6

Start / End Page

29053

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • TRPV Cation Channels
  • Severity of Illness Index
  • Osteoarthritis
  • Mice, Knockout
  • Mice
  • Menisci, Tibial
  • Mechanotransduction, Cellular
  • Gene Expression Regulation
  • Chondrocytes
 

Citation

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O’Conor, C. J., Ramalingam, S., Zelenski, N. A., Benefield, H. C., Rigo, I., Little, D., … Guilak, F. (2016). Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis. Sci Rep, 6, 29053. https://doi.org/10.1038/srep29053
O’Conor, Christopher J., Sendhilnathan Ramalingam, Nicole A. Zelenski, Halei C. Benefield, Isaura Rigo, Dianne Little, Chia-Lung Wu, et al. “Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis.Sci Rep 6 (July 8, 2016): 29053. https://doi.org/10.1038/srep29053.
O’Conor CJ, Ramalingam S, Zelenski NA, Benefield HC, Rigo I, Little D, et al. Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis. Sci Rep. 2016 Jul 8;6:29053.
O’Conor, Christopher J., et al. “Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis.Sci Rep, vol. 6, July 2016, p. 29053. Pubmed, doi:10.1038/srep29053.
O’Conor CJ, Ramalingam S, Zelenski NA, Benefield HC, Rigo I, Little D, Wu C-L, Chen D, Liedtke W, McNulty AL, Guilak F. Cartilage-Specific Knockout of the Mechanosensory Ion Channel TRPV4 Decreases Age-Related Osteoarthritis. Sci Rep. 2016 Jul 8;6:29053.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

July 8, 2016

Volume

6

Start / End Page

29053

Location

England

Related Subject Headings

  • Transforming Growth Factor beta1
  • TRPV Cation Channels
  • Severity of Illness Index
  • Osteoarthritis
  • Mice, Knockout
  • Mice
  • Menisci, Tibial
  • Mechanotransduction, Cellular
  • Gene Expression Regulation
  • Chondrocytes