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Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus.

Publication ,  Journal Article
McNulty, AL; Weinberg, JB; Guilak, F
Published in: Clin Orthop Relat Res
June 2009

Damage or injury of the meniscus is associated with onset and progression of knee osteoarthritis (OA). The intrinsic repair capacity of the meniscus is inhibited by inflammatory cytokines, such as interleukin-1 (IL-1). Using an in vitro meniscal repair model system, we examined the hypothesis that inhibition of matrix metalloproteinases (MMPs) in the presence of IL-1 will enhance repair of meniscal lesions. Integrative repair of the meniscus was examined between two concentric explants cultured with IL-1 and various MMP inhibitors for 14 days. Throughout the culture period, we assessed total specific MMP activity in the media. At harvest, biomechanical testing to assess the strength of repair and histologic staining were performed. IL-1 decreased the shear strength of repair, as compared with control explants. In the presence of IL-1, the broad-spectrum MMP inhibitor GM 6001 decreased the MMP activity in the media, increased the shear strength of repair, and enhanced tissue repair in the interface. However, individual MMP inhibitors did not alter the shear strength of repair in either the presence or absence of IL-1. These findings suggest IL-1 may inhibit meniscal repair through upregulation of MMPs, but inhibition of multiple MMPs may be necessary to promote integrative meniscal repair.

Duke Scholars

Published In

Clin Orthop Relat Res

DOI

EISSN

1528-1132

Publication Date

June 2009

Volume

467

Issue

6

Start / End Page

1557 / 1567

Location

United States

Related Subject Headings

  • Up-Regulation
  • Swine
  • Sensitivity and Specificity
  • Protease Inhibitors
  • Orthopedics
  • Oligopeptides
  • Menisci, Tibial
  • Matrix Metalloproteinase Inhibitors
  • Interleukin-1
  • In Vitro Techniques
 

Citation

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McNulty, A. L., Weinberg, J. B., & Guilak, F. (2009). Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin Orthop Relat Res, 467(6), 1557–1567. https://doi.org/10.1007/s11999-008-0596-6
McNulty, Amy L., J Brice Weinberg, and Farshid Guilak. “Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus.Clin Orthop Relat Res 467, no. 6 (June 2009): 1557–67. https://doi.org/10.1007/s11999-008-0596-6.
McNulty AL, Weinberg JB, Guilak F. Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin Orthop Relat Res. 2009 Jun;467(6):1557–67.
McNulty, Amy L., et al. “Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus.Clin Orthop Relat Res, vol. 467, no. 6, June 2009, pp. 1557–67. Pubmed, doi:10.1007/s11999-008-0596-6.
McNulty AL, Weinberg JB, Guilak F. Inhibition of matrix metalloproteinases enhances in vitro repair of the meniscus. Clin Orthop Relat Res. 2009 Jun;467(6):1557–1567.
Journal cover image

Published In

Clin Orthop Relat Res

DOI

EISSN

1528-1132

Publication Date

June 2009

Volume

467

Issue

6

Start / End Page

1557 / 1567

Location

United States

Related Subject Headings

  • Up-Regulation
  • Swine
  • Sensitivity and Specificity
  • Protease Inhibitors
  • Orthopedics
  • Oligopeptides
  • Menisci, Tibial
  • Matrix Metalloproteinase Inhibitors
  • Interleukin-1
  • In Vitro Techniques