Nitric oxide enhances collagen synthesis in cultured human tendon cells

J Orthop Res. 2006 Feb;24(2):159-72. doi: 10.1002/jor.20060.


Collagen deposition is an important process that occurs during wound healing. We and others have shown that nitric oxide (NO) is important in tendon healing. The mechanisms whereby healing is enhanced are, however, undetermined. The aim of this study was to investigate whether NO could enhance collagen synthesis in cultured human tendon cells via exogenous NO and via an adenovirus containing the gene for inducible nitric oxide synthase (Ad-iNOS). Tendon cells from the torn edge of the tendons of patients undergoing rotator cuff repair surgery were cultured following collagenase digestion, and stimulated with exogenous NO (SNAP), transfected with Ad-iNOS, and treated with the NOS inhibitor, L-NMMA. Total protein and collagen synthesis were evaluated by (3)H-proline and collagenase sensitive (3)H-proline incorporation in human tendon cells. High doses of exogenous NO (SNAP) inhibited collagen synthesis. Lower doses enhanced total protein and collagen synthesis of the tendon cells. Ad-iNOS successfully transfected active iNOS into human tendon cells in vitro and also enhanced total protein and collagen synthesis of the tendon cells. The NOS inhibitor, L-NMMA, inhibited the effects of iNOS on the cells. Our studies show for first time that nitric oxide can enhance collagen synthesis in human tendon cells in vitro. These results may explain, in part, at least, the beneficial effects of NO donors in animal models and during the treatment of tendonopathies in human clinical trials. .

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics
  • Aged
  • Cell Survival / drug effects
  • Cells, Cultured
  • Collagen / biosynthesis*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / pharmacology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Nitric Oxide / pharmacology*
  • Nitric Oxide Donors / pharmacology
  • Nitric Oxide Synthase Type II / antagonists & inhibitors
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • Rotator Cuff / cytology
  • Rotator Cuff / drug effects*
  • Rotator Cuff / enzymology
  • S-Nitroso-N-Acetylpenicillamine / pharmacology
  • Transfection
  • omega-N-Methylarginine / pharmacology


  • Enzyme Inhibitors
  • Nitric Oxide Donors
  • omega-N-Methylarginine
  • Nitric Oxide
  • S-Nitroso-N-Acetylpenicillamine
  • Collagen
  • Nitric Oxide Synthase Type II