Decreased proliferation of aging tenocytes is associated with down-regulation of cellular senescence-inhibited gene and up-regulation of p27

J Orthop Res. 2011 Oct;29(10):1598-603. doi: 10.1002/jor.21418. Epub 2011 Mar 30.

Abstract

Symptomatic tendinopathy tends to be age-related. However, the molecular mechanisms of ageing and its effects on tenocyte proliferation and cell cycle progression are unknown. We examined tenocytes from Achilles tendons in rats from three age groups (young, 2 months; middle-aged, 12 months, and near senescence, 24 months). Tenocyte proliferation was assessed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. Senescence-associated β-galactosidase (SA β-gal) staining was performed in all groups of tenocytes. mRNA and protein expression of cellular senescence-inhibited gene (CSIG) and p27 was measured by reverse transcription-polymerase chain reaction (RT-PCR) and Western blot, respectively. The results of MTT assay revealed that tenocyte proliferation decreased with age (p < 0.05). Cell cycle progression was arrested at G0/G1 phase in senescent tenocytes. More senescent tenocytes expressed SA β-gal than young tenocytes did. By RT-PCR and Western blot analysis, the gene and protein expression of CSIG was found to be down-regulated, whereas that of p27 was up-regulated with age. In conclusion, the proliferation of tenocytes declines with age and is associated with the down-regulation of CSIG and up-regulation of p27.

MeSH terms

  • Achilles Tendon / cytology*
  • Achilles Tendon / metabolism
  • Aging / metabolism*
  • Animals
  • Cell Proliferation*
  • Cells, Cultured
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Flow Cytometry
  • Gene Expression Regulation
  • Rats
  • Rats, Sprague-Dawley
  • beta-Galactosidase / metabolism

Substances

  • Cyclin-Dependent Kinase Inhibitor p27
  • beta-Galactosidase