Physiology and pathophysiology of nitrosative and oxidative stress in osteoarthritic joint destruction

Can J Physiol Pharmacol. 2011 Jul;89(7):455-66. doi: 10.1139/y11-055. Epub 2011 Jul 27.


Osteoarthritis (OA) is one of the most common chronic diseases, with increasing importance due to increased life expectancy. On a cellular level, the pathophysiology of joint function impairment and ultimate destruction associated with OA remains poorly understood. Free radicals are highly reactive molecules involved in both normal intracellular signal transduction and degenerative cellular processes. An imbalance between the free radical burden and cellular scavenging mechanisms, defined as oxidative stress, has been identified as a relevant factor in OA pathogenesis. This literature review elucidates the involvement of nitrosative and oxidative stress in cellular ageing in joints, cell senescence, and apoptosis. Free radical exposure is known to promote cellular senescence and apoptosis, and the involvement of radical oxygen species (ROS) in inflammation, fibrosis control, and pain nociception has been proven. A relatively novel approach to OA pathophysiology considers the joint to be a dynamic system consisting of 3, continuously interacting compartments, cartilage, synovial tissue, and subchondral bone. Current knowledge concerning free radical involvement in paracrine signalling in OA is reviewed. The interrelationship between oxidative imbalances and OA pathophysiology may provide a novel approach to the comprehension, and therefore modification, of OA disease progression and symptom control.

Publication types

  • Review

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Cellular Senescence / physiology
  • Free Radicals / metabolism
  • Humans
  • Nitric Oxide / metabolism*
  • Nitrosation
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Osteoarthritis / physiopathology*
  • Oxidative Stress / physiology*
  • Reactive Oxygen Species / metabolism*


  • Free Radicals
  • Reactive Oxygen Species
  • Nitric Oxide