Glucocorticoids inhibit tenocyte proliferation and Tendon progenitor cell recruitment

Authors

  • Nanette Scutt,

    1. Sheffield Centre for Sports Medicine, Division of Clinical Sciences South, University of Sheffield Medical School, Sheffield, United Kingdom
    2. Tissue Engineering Group, Department of Engineering Materials, University of Sheffield, Sir Robert Hadfield Building, Mappin Street, Sheffield S1 3JD, United Kingdom
    Search for more papers by this author
  • Christer G. Rolf,

    1. Sheffield Centre for Sports Medicine, Division of Clinical Sciences South, University of Sheffield Medical School, Sheffield, United Kingdom
    Search for more papers by this author
  • Andrew Scutt

    Corresponding author
    1. Sheffield Centre for Sports Medicine, Division of Clinical Sciences South, University of Sheffield Medical School, Sheffield, United Kingdom
    2. Tissue Engineering Group, Department of Engineering Materials, University of Sheffield, Sir Robert Hadfield Building, Mappin Street, Sheffield S1 3JD, United Kingdom
    • Sheffield Centre for Sports Medicine, Division of Clinical Sciences South, University of Sheffield Medical School, Sheffield, United Kingdom. Telephone: 0114 222 6025; Fax: 0114 222 5943
    Search for more papers by this author

Abstract

Corticosteroid injection is commonly used to treat tendon injuries but is often associated with tendon rupture and impaired tendon healing. The effects of dexamethasone on tenocytes have been studied in vitro but only using high concentrations of dexamethasone in monolayer cultures of tenocytes over short periods of time. We have therefore investigated the effects of physiological and pharmacological concentrations of dexamethasone on monolayer cultures of tenocytes over extended time periods. We have also used fibroblastic-colony forming unit cultures to examine the effects of dexamethasone on a progenitor cell population located in tendons. Culturing tenocytes in the presence of dexamethasone for a period of 24 days resulted in a concentration-related decrease in cell number and collagen synthesis as compared to control cultures. This effect was time dependent with cell number in both dexamethasone-treated and control cultures leveling off after 14 days with the control cultures reaching higher cell densities. In contrast in control cultures, collagen accumulation continued to increase until week 4, whereas in the presence of dexamethasone, this tended to level off after 14 days. To study the role of progenitor cell recruitment, the effects of dexamethasone were investigated using the fibroblastic-colony forming unit assay. Treatment with dexamethasone at concentrations of 0.1 nM to 10 µM leads to a progressive reduction in mean colony size as compared to control cultures. Colony number remained constant at concentrations below 10 nM but fell progressively at concentrations above this. In conclusion, dexamethasone reduces both cell number and collagen synthesis in tenocyte cultures in a concentration-dependent manner by both direct effects on tenocyte proliferation and collagen accumulation, and also by modulating the recruitment of tendon progenitor cells. © 2005 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

Ancillary