Synoviocyte apoptosis may differentiate responder and non-responder patients to methotrexate treatment in rheumatoid arthritis

다국어 초록 (Multilingual Abstract)

We aimed to evaluate whether methotrexate(MTX) in vitro induces apoptosis in synoviocytes obtainedfrom rheumatoid arthritis patients and whether the apoptosisinducing effect of MTX to synoviocytes is correlatedwith the clinical responsiveness to MTX in patients withrheumatoid arthritis (RA). We evaluated 18 patients withRA taking MTX 15–20 mg/week as the subject group (nineresponders and nine non-responders) and ten patients withosteoarthritis (OA) and nine patients with ankylosingspondylitis (AS) as the control group. Synoviocytes, culturedfrom the synovial fluid of the knee joint of eachsubject, were used for experiments between passages 4 and6, and were treated with MTX. The induction of apoptosiswas determined by the quantification of DNA hypoploidyby flow cytometry, nuclear morphology, caspases activation,DNA electrophoresis, and mitochondrial membranepotential measurements. The viability of synoviocytes treated with MTX was different between the MTXresponders and nonresponders. MTX induced apoptosis incultured synoviocytes by mitochondria- and caspasedependentmanners in the MTX responders but did not inthe MTX non-responder, OA, and AS patients. The apoptoticresponsiveness of the synoviocytes to MTX predictsthe sensitivity to MTX treatment and provides a methoddetermine the early application of an anti-tumor necrosisfactor-a agent in RA treatment.

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