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Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro.

Publication ,  Journal Article
Wilusz, RE; Weinberg, JB; Guilak, F; McNulty, AL
Published in: J Orthop Res
April 2008

Damage or loss of the meniscus is associated with progressive osteoarthritic degeneration of the knee joint. Injured and degenerative joints are characterized by elevated levels of the pro-inflammatory cytokine interleukin-1 (IL-1), which with prolonged exposure can induce catabolic and anti-anabolic activities that inhibit tissue repair. We used an in vitro model system to examine the hypotheses that acute exposure to IL-1 inhibits meniscal repair, and that an IL-1-mediated increase in matrix metalloproteinase (MMP) activity is associated with the inhibition of repair. Integrative tissue repair was studied between concentric explants of porcine medial menisci that were treated with IL-1alpha acutely (100 pg/mL for 1 or 3 days) or chronically (100 pg/mL for entire culture duration). After 14 and 28 days in culture, biomechanical testing, cell viability, and histology were performed to assess meniscal repair. Total specific MMP activity in the culture media was measured using a quenched fluorescent substrate. As little as 1 day of IL-1 exposure significantly reduced shear strength, cell accumulation, and tissue repair compared to controls. IL-1 exposure for 1 or 3 days significantly increased MMP activity that subsided by day 9. With chronic IL-1 exposure, MMP activity remained elevated for the duration of culture and was negatively correlated with repair strength. Our study shows that short-term exposure to physiologically relevant concentrations of IL-1 significantly reduces meniscal repair in vitro, and thus may potentially inhibit the intrinsic repair response in vivo. The suppression of IL-1 or MMP expression and/or activity warrant investigation as potential strategies for promoting meniscal repair.

Duke Scholars

Published In

J Orthop Res

DOI

EISSN

1554-527X

Publication Date

April 2008

Volume

26

Issue

4

Start / End Page

504 / 512

Location

United States

Related Subject Headings

  • Wound Healing
  • Tissue Culture Techniques
  • Swine
  • Shear Strength
  • Orthopedics
  • Microscopy, Fluorescence
  • Microscopy, Confocal
  • Menisci, Tibial
  • Matrix Metalloproteinases
  • Interleukin-1
 

Citation

APA
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ICMJE
MLA
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Wilusz, R. E., Weinberg, J. B., Guilak, F., & McNulty, A. L. (2008). Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro. J Orthop Res, 26(4), 504–512. https://doi.org/10.1002/jor.20538
Wilusz, Rebecca E., J Brice Weinberg, Farshid Guilak, and Amy L. McNulty. “Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro.J Orthop Res 26, no. 4 (April 2008): 504–12. https://doi.org/10.1002/jor.20538.
Wilusz RE, Weinberg JB, Guilak F, McNulty AL. Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro. J Orthop Res. 2008 Apr;26(4):504–12.
Wilusz, Rebecca E., et al. “Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro.J Orthop Res, vol. 26, no. 4, Apr. 2008, pp. 504–12. Pubmed, doi:10.1002/jor.20538.
Wilusz RE, Weinberg JB, Guilak F, McNulty AL. Inhibition of integrative repair of the meniscus following acute exposure to interleukin-1 in vitro. J Orthop Res. 2008 Apr;26(4):504–512.
Journal cover image

Published In

J Orthop Res

DOI

EISSN

1554-527X

Publication Date

April 2008

Volume

26

Issue

4

Start / End Page

504 / 512

Location

United States

Related Subject Headings

  • Wound Healing
  • Tissue Culture Techniques
  • Swine
  • Shear Strength
  • Orthopedics
  • Microscopy, Fluorescence
  • Microscopy, Confocal
  • Menisci, Tibial
  • Matrix Metalloproteinases
  • Interleukin-1