Oral administration of N-acetyl cysteine prevents osteoarthritis development and progression in a rat model

Abstract

The number of osteoarthritis patients is increasing with the rise in the number of elderly people in developed countries. Osteoarthritis, which causes joint pain and deformity leading to loss of activities of daily living, is often treated surgically. Here we show that mechanical stress promotes accumulation of reactive oxygen species (ROS) in chondrocytes in vivo, resulting in chondrocyte apoptosis and leading to osteoarthritis development in a rat model. We demonstrate that mechanical stress induces ROS accumulation and inflammatory cytokine expression in cultured chondrocytes in vitro and that both are inhibited by treatment with the anti-oxidant N-acetyl cysteine (NAC). In vivo, osteoarthritis development in a rat osteoarthritis model was also significantly inhibited by oral administration of NAC. MMP13 expression and down-regulation of type II collagen in chondrocytes, both of which indicate osteoarthritis, as well as chondrocyte apoptosis in osteoarthritis rats were inhibited by NAC. Interestingly, osteoarthritis development in sham-operated control sides, likely due to disruption of normal weight-bearing activity on the control side, was also significantly inhibited by NAC. We conclude that osteoarthritis development in rats is significantly antagonized by oral NAC administration. Currently, no oral medication is available to prevent osteoarthritis development. Our work suggests that NAC may represent such a reagent and serve as osteoarthritis treatment.

Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species

“…Taken together, our results confirm the therapeutic potential of inhibiting ROS to treat OA. Indeed, it has already been demonstrated that oral administration of the anti-oxidant N-acetyl cysteine (NAC) protects against OA in the rat [ 32 ] and reduces hypertrophy in the growth plate of mice [ 28 ]. Future studies could use NAC to evaluate its impact on oxPTM-CII generation, hypertrophy, and OA initiation and progression in animal models.…”

Early detection of osteoarthritis in the rat with an antibody specific to type II collagen modified by reactive oxygen species

“…This study together with results from others con rms the therapeutic potential of inhibiting ROS to treat OA. Indeed, it was demonstrated that oral administration of the anti-oxydant N-acetyl cysteine (NAC) protect against OA in the rat (32) and reduces hypertrophy in the growth plate of mice (28). Future studies could use NAC to evaluate its impact on oxPTM-CII generation, hypertrophy and OA initiation and progression in animal models.…”

N-Acetyl Cysteine Modulates the Inflammatory and Oxidative Stress Responses of Rescued Growth-Arrested Dental Pulp Microtissues Exposed to TEGDMA in ECM

“…NAC was capable of protecting the mature microtissues from the deteriorating effect of the monomer. This ability of NAC to defend tissues and their components from destruction is relatable to its roles in preventing oxidative degradation of biological membranes and/or degradation of MMPs [ 60 , 61 ].…”