Background there is no study reporting whether MTX inhibits rheumatoid synovitis by inducing apoptosis of synoviocytes, depending on the clinical sensitivity of MTX.
Objectives We aimed to evaluate whether MTX in vitro induces apoptosis in synoviocytes obtained from rheumatoid arthritis patients and whether the apoptosis inducing effect of MTX to synoviocytes is correlated with the clinical responsiveness to MTX in patients with RA.
Methods We evaluated 10 patients with RA taking MTX 15-20 mg/week as the subject group (5 responders and 5 non-responders) and 5 patients with osteoarthritis (OA) and 3 patients with ankylosing spondylitis (AS) as the control group. Synoviocytes, cultured from the synovial fluid of the knee joint of each subject, were used for experiments between passages 4 and 6, and were treated with MTX. The induction of apoptosis was determined by the quantification of DNA hypoploidy by flow cytometry, nuclear morphology, caspases activation, DNA electrophoresis, and mitochondrial membrane potential measurements.
Results The viability of synoviocytes treated with MTX was different between the MTX responders and nonresponders. MTX induced apoptosis in cultured synoviocytes by mitochondria- and caspase-dependent manners in the MTX responders but did not in the MTX non-responder, OA, and AS patients.
Conclusions The apoptotic responsiveness of the synoviocytes to MTX predicts the sensitivity to MTX treatment and provides a method determine the early application of TNF-α agent in RA treatment.
Wessels JA, et al(2008) Rheumatology 47, 249-55
Disclosure of Interest None Declared