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Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage.

Publication ,  Journal Article
Zelenski, NA; Leddy, HA; Sanchez-Adams, J; Zhang, J; Bonaldo, P; Liedtke, W; Guilak, F
Published in: Arthritis Rheumatol
May 2015

OBJECTIVE: Mechanical factors play a critical role in the physiology and pathology of articular cartilage, although the mechanisms of mechanical signal transduction are not fully understood. We undertook this study to test the hypothesis that type VI collagen is necessary for mechanotransduction in articular cartilage by determining the effects of type VI collagen knockout on the activation of the mechano-osmosensitive, calcium-permeable channel TRPV4 (transient receptor potential vanilloid channel 4) as well as on osmotically induced chondrocyte swelling and pericellular matrix (PCM) mechanical properties. METHODS: Confocal laser scanning microscopy was used to image TRPV4-mediated calcium signaling and osmotically induced cell swelling in intact femora from 2- and 9-month-old wild-type (WT) and type VI collagen-deficient (Col6a1(-/-)) mice. Immunofluorescence-guided atomic force microscopy was used to map PCM mechanical properties based on the presence of perlecan. RESULTS: Hypo-osmotic stress-induced TRPV4-mediated calcium signaling was increased in Col6a1(-/-) mice relative to WT controls at 2 months. Col6a1(-/-) mice exhibited significantly increased osmotically induced cell swelling and decreased PCM moduli relative to WT controls at both ages. CONCLUSION: In contrast to our original hypothesis, type VI collagen was not required for TRPV4-mediated Ca(2+) signaling; however, knockout of type VI collagen altered the mechanical properties of the PCM, which in turn increased the extent of cell swelling and osmotically induced TRPV4 signaling in an age-dependent manner. These findings emphasize the role of the PCM as a transducer of mechanical and physicochemical signals, and they suggest that alterations in PCM properties, as may occur with aging or osteoarthritis, can influence mechanotransduction via TRPV4 or other ion channels.

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Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

May 2015

Volume

67

Issue

5

Start / End Page

1286 / 1294

Location

United States

Related Subject Headings

  • TRPV Cation Channels
  • Osmotic Pressure
  • Microscopy, Confocal
  • Mice, Knockout
  • Mice
  • Mechanotransduction, Cellular
  • Heparan Sulfate Proteoglycans
  • Extracellular Matrix
  • Collagen Type VI
  • Chondrocytes
 

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Zelenski, N. A., Leddy, H. A., Sanchez-Adams, J., Zhang, J., Bonaldo, P., Liedtke, W., & Guilak, F. (2015). Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage. Arthritis Rheumatol, 67(5), 1286–1294. https://doi.org/10.1002/art.39034
Zelenski, Nicole A., Holly A. Leddy, Johannah Sanchez-Adams, Jinzi Zhang, Paolo Bonaldo, Wolfgang Liedtke, and Farshid Guilak. “Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage.Arthritis Rheumatol 67, no. 5 (May 2015): 1286–94. https://doi.org/10.1002/art.39034.
Zelenski NA, Leddy HA, Sanchez-Adams J, Zhang J, Bonaldo P, Liedtke W, et al. Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage. Arthritis Rheumatol. 2015 May;67(5):1286–94.
Zelenski, Nicole A., et al. “Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage.Arthritis Rheumatol, vol. 67, no. 5, May 2015, pp. 1286–94. Pubmed, doi:10.1002/art.39034.
Zelenski NA, Leddy HA, Sanchez-Adams J, Zhang J, Bonaldo P, Liedtke W, Guilak F. Type VI Collagen Regulates Pericellular Matrix Properties, Chondrocyte Swelling, and Mechanotransduction in Mouse Articular Cartilage. Arthritis Rheumatol. 2015 May;67(5):1286–1294.
Journal cover image

Published In

Arthritis Rheumatol

DOI

EISSN

2326-5205

Publication Date

May 2015

Volume

67

Issue

5

Start / End Page

1286 / 1294

Location

United States

Related Subject Headings

  • TRPV Cation Channels
  • Osmotic Pressure
  • Microscopy, Confocal
  • Mice, Knockout
  • Mice
  • Mechanotransduction, Cellular
  • Heparan Sulfate Proteoglycans
  • Extracellular Matrix
  • Collagen Type VI
  • Chondrocytes