title: Synoviocyte apoptosis may differentiate responder and non-responder patients to methotrexate treatment in rheumatoid arthritis.
abstract: We aimed to evaluate whether methotrexate (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 rheumatoid arthritis (RA). We evaluated 18 patients with RA taking MTX 15-20 mg/week as the subject group (nine responders and nine non-responders) and ten patients with osteoarthritis (OA) and nine 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. 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. The apoptotic responsiveness of the synoviocytes to MTX predicts the sensitivity to MTX treatment and provides a method determine the early application of an anti-tumor necrosis factor-α agent in RA treatment.
authors.affiliation: Division of Rheumatology Department of Internal Medicine, Dong-A University, Pusan, Republic of Korea, harrison1007@hanmail.net.
authors.forename: Sang Yeob
authors.initials: SY
authors.lastname: Lee
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Park
authors.forename: Sung Won
authors.initials: SW
authors.lastname: Lee
authors.forename: Sang Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Min Kyeong
authors.initials: MK
authors.lastname: Son
authors.forename: Yung Hyun
authors.initials: YH
authors.lastname: Choi
authors.forename: Won Tae
authors.initials: WT
authors.lastname: Chung
authors.forename: Young Hyun
authors.initials: YH
authors.lastname: Yoo
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000503:physiopathology; D016022:Case-Control Studies; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008727:Methotrexate / Q000494:pharmacology* / Q000627:therapeutic use; D008875:Middle Aged; D010003:Osteoarthritis / Q000188:drug therapy; D013167:Spondylitis, Ankylosing / Q000188:drug therapy / Q000503:physiopathology; D013583:Synovial Membrane / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D008727:Methotrexate