Evidence of the TNF-α system in the human Achilles tendon: expression of TNF-α and TNF receptor at both protein and mRNA levels in the tenocytes

Cells Tissues Organs. 2012;196(4):339-52. doi: 10.1159/000335475. Epub 2012 May 8.


Understanding adaption to load is essential for prevention and treatment of tendinopathy/tendinosis. Cytokine release in response to load is one mechanism involved in mechanotransduction. The cytokine tumor necrosis factor alpha (TNF-α) is implicated in tendinosis and can induce apoptotic effects via tumor necrosis factor receptor 1 (TNFR1). The complete absence of information concerning the TNF-α system in Achilles tendon is a limitation as mid-portion Achilles tendinosis is very frequent.

Purpose: To examine expression patterns of TNF-α and its two receptors (TNFR1 and TNFR2) in human Achilles tendinosis and control tissue and to biochemically confirm the presence of TNF-α in tendinosis tissue.

Methods: TNF-α and TNFR1 mRNA were detected via in situ hybridization. TNF-α, TNFR1, and TNFR2 were demonstrated immunohistochemically. Apoptosis markers were utilized. ELISA was used to detect TNF-α.

Results: TNF-α and TNFR1 mRNA was detected in tenocytes of both tendinosis and control tendons. Tenocytes from both groups displayed specific immunoreactions for TNF-α, TNFR1, and TNFR2. The widened/rounded tenocytes of tendinosis samples exhibited the most intense immunoreactions. Apoptosis was detected in only a subpopulation of the tenocytes in tendinosis tissue. TNF-α was measurable in tendinosis tissue. Inflammatory cells were not seen.

Conclusion: This is the first evidence of the existence of the TNF-α system in the human Achilles tendon. Findings are confirmed at mRNA and protein levels as well as biochemically. The TNF-α system was in principle confined to the tenocytes. The connection between tenocyte morphology and the expression pattern of TNF-α, TNFR1, and TNFR2 suggests that the TNF-α system may be involved in tenocyte activation in Achilles tendinosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achilles Tendon / metabolism*
  • Achilles Tendon / pathology
  • Apoptosis
  • Biopsy
  • Cytokines / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Male
  • Middle Aged
  • RNA, Messenger / biosynthesis*
  • RNA, Messenger / genetics
  • Receptors, Tumor Necrosis Factor / biosynthesis*
  • Receptors, Tumor Necrosis Factor / genetics
  • Receptors, Tumor Necrosis Factor / metabolism
  • Tendinopathy / genetics
  • Tendinopathy / metabolism*
  • Tendinopathy / pathology
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism


  • Cytokines
  • RNA, Messenger
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha