Beneficial Effect of Tempol, a Membrane-Permeable Radical Scavenger, on Inflammation and Osteoarthritis in In Vitro Models

Osteoarthritis (OA) is one of the most common and widespread diseases which is highly disabling for humans. This makes OA a chronic disease for which it is urgent to find new therapeutic strategies. The inflammatory state in OA contributes to its progression through multiple mechanisms involving the recruitment of phagocytes and leukocytes, inflammatory response, and reactive oxygen species (ROS) production. Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) is classifiable as a piperidine nitroxide, with excellent antioxidant effects, while its anti-inflammatory role is not yet clear. On this basis, we explored its promising biological properties in two in vitro model:, macrophage (J774) and chondrocyte (CC) cell lines. With this aim in mind, we induced inflammation in J774 and CC using lipopolysaccharide (LPS) and Interleukin1β (IL-1β), and after 24, 72 and 168 h of tempol treatment analyzed their effects on cytotoxicity and anti-inflammatory activity. Our data suggested that tempol treatment is able to reduce inflammation and nitrite production in LPS-induced J774 as well as reducing the production of proinflammatory mediators including cytokines, enzymes, and metalloproteases (MMPs) in IL-1β-stimulated CC. Thus, since inflammation and oxidative stress have a crucial role in the pathogenesis and progression of OA, tempol could be considered as a new therapeutic approach for this pathology.