Sirtuin 1 (
Sirt1) is a nuclear
enzyme from the class III
histone deacetylases that modulates gene expression and is involved in bone and cartilage remodeling. The goal of our study was to evaluate
Sirt1 activity in peripheral blood mononuclear cells in patients with
osteoarthritis in comparison with control patients, and to determine the relationship between
Sirt1 activity and production of TNFα,
IL-6 and
IL-8 by peripheral blood mononuclear cells after ex vivo treatment with
resveratrol, a
Sirt1 activator.
RESULTS: A prospective study was performed to compare the activity of
Sirt1 in patients with primary
osteoarthritis of the knee (American College of Rheumatology criteria) with its activity in controls. Peripheral blood mononuclear cells were isolated from peripheral blood, and
Sirt1 activity evaluated from cytoplasmic and nuclear compartments using a fluorometric assay. Culture supernatant levels of TNFα,
IL-6, and
IL-8 were quantified before and after
resveratrol ex vivo treatment. Nineteen patients with symptomatic
knee osteoarthritis (age 64 ±9 years) and 18 controls (age 54 ±13 years) were included. No differences were found in cytoplasmic or nuclear
Sirt1 activity between patients and controls. After
resveratrol treatment, no changes in TNFα or
IL-8 levels were found, but a significant dose-dependent increase in
IL-6 levels was demonstrated in patients with
osteoarthritis, but not controls.
Sirt1 activity did not correlate with clinical activity (Lequesne's index) or
inflammation (erythrocyte sedimentation rate,
C-reactive protein).
CONCLUSION:
Sirt1 activity (cytoplasmic and nuclear) from peripheral blood mononuclear cells did not differ between patients with
osteoarthritis and controls. Ex vivo treatment of peripheral blood mononuclear cells with
resveratrol was associated with a dose-dependent increase in
IL-6 levels only in patients with
osteoarthritis.