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Menisci of the rabbit knee require mechanical loading to maintain homeostasis: cyclic hydrostatic compression in vitro prevents derepression of catabolic genes

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Journal of Orthopaedic Science

Abstract

Background

The purpose of this study was to examine the influence of removing menisci from their in vivo loading environment on gene expression patterns and to determine whether in vitro loading can maintain the tissues in their in vivo phenotype.

Methods

Lateral and medial rabbit meniscal explants from one leg were cultured in vitro and subjected to intermittent cyclic hydrostatic pressure (CHP) of 1 MPa at 0.5 Hz for 1 min and a rest period of 14 min (4 h of culture). The contralateral menisci were incubated at atmospheric pressure for 4 h. Menisci from both legs of another set of rabbits were frozen immediately to yield time zero values reflective of in vivo mRNA levels. Total RNA was isolated from all groups and processed for reverse transcription-polymerase chain reaction analysis for a subset of relevant genes (matrix molecules, cytokines, proteinases and inhibitors, enzymes).

Results

It was found that mRNA levels for MMP-1, MMP-3, TIMPs, iNOS, COX-2, interleukin-1β in both menisci, and interleukin-6 in medial menisci were significantly elevated in tissues cultured under nonloading conditions compared to the time zero controls. Subjecting menisci to CHP significantly prevented these increases in mRNA levels for nearly all of the indicated molecules. In contrast, there were no significant differences in mRNA levels for collagens, biglycan, MMP-13, or TIMP-4 between the time zero values and those cultured under either nonloading or loading conditions.

Conclusions

These studies demonstrate that removing rabbit menisci from their normal in vivo mechanical environment leads to an apparent up-regulation of a subset of potent effector molecules that could mediate catabolic activities, and that in vitro CHP can largely prevent this apparent up-regulation.

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Osaka Rosai Hospital, Osaka, Japan

    Takashi Natsu-ume

  2. Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    Tokifumi Majima

  3. McCaig Centre for Joint Injury and Arthritis Research, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, T2N 4N1, Canada

    Carol Reno, Nigel G. Shrive, Cyril B. Frank & David A. Hart

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  1. Takashi Natsu-ume
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  2. Tokifumi Majima
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  3. Carol Reno
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  4. Nigel G. Shrive
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  5. Cyril B. Frank
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  6. David A. Hart
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Natsu-ume, T., Majima, T., Reno, C. et al. Menisci of the rabbit knee require mechanical loading to maintain homeostasis: cyclic hydrostatic compression in vitro prevents derepression of catabolic genes. J Orthop Sci 10, 396–405 (2005). https://doi.org/10.1007/s00776-005-0912-x

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  • DOI: https://doi.org/10.1007/s00776-005-0912-x

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