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Loss of Homeostatic Strain Alters Mechanostat “Set Point” of Tendon Cells In Vitro

  • Symposium: Molecular and Clinical Developments in Tendinopathy
  • Published:
Clinical Orthopaedics and Related Research

Abstract

Tendon cells respond to mechanical loads. The character (anabolic or catabolic) and sensitivity of this response is determined by the mechanostat set point of the cell, which is governed by the cytoskeleton and its interaction with the extracellular matrix. To determine if loss of cytoskeletal tension following stress deprivation decreases the mechanoresponsiveness of tendon cells, we cultured rat tail tendons under stress-deprived conditions for 48 hours and then cyclically loaded them for 24 hours at 1%, 3%, or 6% strain at 0.17 Hz. Stress deprivation upregulated MMP-13 mRNA expression and caused progressive loss of cell-matrix contact compared to fresh controls. The application of 1% strain to fresh tendons for 24 hours inhibited MMP-13 mRNA expression compared to stress-deprived tendons over the same period. However, when tendons were stress-deprived for 48 hours and then subjected to the same loading regime, the inhibition of MMP-13 mRNA expression was decreased. In stress-deprived tendons, it was necessary to increase the strain magnitude to 3% to achieve the same level of MMP-13 mRNA inhibition seen in fresh tendons exercised at 1% strain. The data suggest loss of cytoskeletal tension alters the mechanostat set point and decreases the mechanoresponsiveness of tendon cells.

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Acknowledgments

We thank Ralph Commons for his assistance in obtaining the electron photomicrographs.

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Authors and Affiliations

  1. Laboratory for Comparative Orthopaedic Research, College of Veterinary Medicine, G-387, Michigan State University, East Lansing, MI, USA

    Steven P. Arnoczky DVM, Michael Lavagnino PhD, Monika Egerbacher DVM, PhD, Oscar Caballero MS, Keri Gardner MS & Marisa A. Shender

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  1. Steven P. Arnoczky DVM
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  2. Michael Lavagnino PhD
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  3. Monika Egerbacher DVM, PhD
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  4. Oscar Caballero MS
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  5. Keri Gardner MS
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  6. Marisa A. Shender
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Correspondence to Steven P. Arnoczky DVM.

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Each author certifies that his or her institution has approved the animal protocol for this investigation and that all investigations were conducted in conformity with ethical principles of research.

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Arnoczky, S.P., Lavagnino, M., Egerbacher, M. et al. Loss of Homeostatic Strain Alters Mechanostat “Set Point” of Tendon Cells In Vitro. Clin Orthop Relat Res 466, 1583–1591 (2008). https://doi.org/10.1007/s11999-008-0264-x

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