Publications (24) View all
-
Article: DcR3-TL1A signalling inhibits cytokine-induced proliferation of rheumatoid synovial fibroblasts.
[show abstract] [hide abstract]
ABSTRACT: Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, lacks the transmembrane domain of conventional TNFRs in order to be a secreted protein. DcR3 competitively binds and inhibits members of the TNF family, including Fas ligand (FasL), LIGHT and TL1A. We previously reported that TNFα-induced DcR3 overexpression in rheumatoid synovial fibroblasts (RA-FLS) protects the cells from Fas-induced apoptosis and that DcR3 induces VLA-4 expression in THP-1 macrophages to inhibit cycloheximide-induced apoptosis. Meanwhile, recent studies have suggested that DcR3 acting as a ligand directly induces the differentiation of macrophages to osteoclasts. Therefore, in the present study, we analyzed the direct effects of DcR3 as a ligand in RA-FLS. The experiments showed that DcR3 binds to TL1A expressed in RA-FLS resulting in the negative regulation of cell proliferation induced by inflammatory cytokines. DcR3-TL1A signalling may be involved in the pathogenesis of rheumatoid arthritis (RA).International Journal of Molecular Medicine 05/2011; 28(3):423-7. · 1.98 Impact Factor -
Article: DcR3 induces cell proliferation through MAPK signaling in chondrocytes of osteoarthritis.
[show abstract] [hide abstract]
ABSTRACT: Decoy receptor 3 (DcR3), a soluble receptor belonging to the tumor necrosis factor (TNF) receptor superfamily, competitively binds and inhibits the TNF family including Fas-ligand (Fas-L), lymphotoxin-like inducible protein that competes with glycoprotein D for binding herpesvirus entry mediator on T-cells (LIGHT) and TNF-like ligand 1A (TL1A). In this study, we investigated the functions of DcR3 on osteoarthritis (OA) chondrocytes. Expressions of DcR3 in chondrocytes were measured by realtime Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). Expression of DcR3 in sera and joint fluids was measured by enzyme-linked immunosorbent assay (ELISA). Chondrocytes were incubated with DcR3-Fc chimera protein (DcR3-Fc) before induction of apoptosis by Fas-L and apoptosis was detected with terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labelling labeling (TUNEL) staining and Western blotting of caspase 8 and poly (ADP-ribose) polymerase (PARP). Chondrocytes were incubated with DcR3-Fc and the proliferation was analyzed by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST) assay. Phosphorylation of Extracellular Signal-Regulated Kinase (ERK), P38 mitogen-activated protein kinase (MAPK) and Jun N-terminal Kinase (JNK) in chondrocytes was measured by Western blotting after incubation with DcR3-Fc, Mitogen-activated protein kinase kinase (MEK1/2) inhibitor, or P38 MAPK inhibitor. Chondrocytes were treated with DcR3-Fc after pre-incubation with blocking antibody of Fas-L, LIGHT and TL1A, and proliferation or phosphorylation of ERK was analyzed. DcR3 was expressed in OA and normal chondrocytes. DcR3-Fc protects chondrocytes from Fas-induced apoptosis. DcR3-Fc increased chondrocytes proliferation and induced the phosphorylation of ERK specifically. DcR3-induced chondrocytes proliferation was inhibited by pre-incubation of PD098059 or blocking Fas-L antibody. DcR3 increased chondrocytes proliferation in OA chondrocytes, but did not in normal. DcR3 regulates the proliferation of OA chondrocytes via ERK signaling and Fas-induced apoptosis.Osteoarthritis and Cartilage 03/2011; 19(7):903-10. · 3.90 Impact Factor -
Article: Predictors of aggravation of cervical spine instability in rheumatoid arthritis patients: the large joint index.
[show abstract] [hide abstract]
ABSTRACT: Improved rheumatic drugs have provided significant benefits, but activities of daily living are not improved if spinal symptoms are overlooked. Furthermore, the appropriate timing for examining the cervical spine during follow-up is unclear. To evaluate the relations of cervical spine instabilities and an index for cervical spine lesion in rheumatoid arthritis (RA) based on extremity radiographs, we examined preoperative radiographs of 100 RA patients who underwent total knee arthroplasty. Radiographic results for eight large joints (bilateral shoulders, elbows, hips, and knees) were graded as follows: Larsen grade > or = 2 for each joint was scored as 1 point, which we refer to as the "large joint index" (LJI), based on 0-8 points. The associations of radiographic cervical lesions with LJI, Ranawat class, the disease duration, RA drugs, or blood analysis data were evaluated. Atlantoaxial subluxation (AAS) (> or = 5 mm) was found in 45 patients, vertical subluxation (VS) (< or = 13 mm) in 42, a posterior atlantodental interval (PADI) (<14 mm) in 21, and subaxial subluxation (SAS) (> or = 3 mm) in 23. Most patients with a PADI < 14 mm (19/21, 90%) were complicated with both AAS and VS. LJI had a significant association with AAS (P < 0.0001), VS (P < 0.01), and PADI (P < 0.01). The PADI was significantly lower (P < 0.0001) and the LJI was significantly higher (P < 0.01) in patients of Ranawat class II compared to patients of Ranawat class I. The disease duration, age at surgery, and age at onset were also significantly associated with cervical instabilities. PADI should be recognized as a predictor of paralysis with anteroposterior instability and vertical and middle-low cervical spine instability. The LJI proposed in this study has the possibility of being a predictor of cervical lesions. Patients with RA onset at a young age and a long disease duration also have a risk of progression of cervical spine instability.Journal of Orthopaedic Science 07/2010; 15(4):540-6. · 0.84 Impact Factor -
Article: Surgical complications and management of occipitothoracic fusion for cervical destructive lesions in RA patients.
[show abstract] [hide abstract]
ABSTRACT: Retrospective clinical study. The objective of this study is to evaluate the clinical outcome of occipitothoracic fusion for severe destructive cervical lesions in rheumatoid arthritis (RA) patients with myelopathy and/or occipitocervical pain, and to discuss surgical complications. The complication rates are compared between 2 groups treated with different instrumentation techniques. Few studies have reported on the results of occipitothoracic fusion in RA patients. In this study, 56 RA patients with myelopathy and/or occipitocervical pain caused by destructive cervical lesions were studied. The patients were divided into 2 groups A and B, according to the used rod diameter and the application of the cervical pedicle screw system. Group A included 38 patients treated with Unit rods (4.75 mm). Group B included 18 patients treated with cervical pedicle screw system (3.2 mm or 3.5 mm diameter rod). Clinical results and surgical complications were evaluated. Mean follow-up time was 36.2 months. Fifteen patients died during follow-up at the mean age of 67.3 years. None died from their cervical lesions. The neurologic status in 46 patients (82%) had improved at least 1 class in the modified Ranawat scale. Perioperative complications occurred in 16 (28.6%), thoracic spine lesions in 11 (19.6%), implant failure in 13 (23.2%), and surgical site infection in 8 (14.3%). There was a tendency for more fractures and pedicle screw pullouts at the lowest level of the fusion area to occur in group B. The neurologic improvement of patients undergoing occipitothoracic fusion after becoming unable to sit owing to their neurologic deficit was poor. The current study suggests that occipitothoracic fusion for rheumatoid destructive cervical lesions can be effective in improving neurologic deficit if performed while patients can still sit. Improvements to methodology of this surgery can be made.Journal of spinal disorders & techniques 04/2010; 23(2):121-6. · 1.21 Impact Factor -
Article: Decoy receptor 3 is highly expressed in patients with rheumatoid arthritis.
[show abstract] [hide abstract]
ABSTRACT: Decoy receptor 3 (DcR3), a member of the tumor necrosis factor receptor (TNFR) superfamily, is a soluble receptor that binds to the TNF family including Fas ligand (Fas-L), LIGHT, and TL1A. DcR3 is mostly expressed in tumor cells and competitively inhibits the TNF family. We previously demonstrated that overexpressed DcR3 in rheumatoid synovial cells protects the cells from apoptosis in vitro. The objective of the study was to investigate DcR3 expression in serum and joint fluids of patients with rheumatoid arthritis (RA) and osteoarthritis (OA), and to analyze the correlations with disease activities and TNFalpha expression. Sera and joint fluids were collected from patients with RA and OA. Expression of DcR3 in sera and joint fluids was measured by ELISA. The concentration of DcR3 in sera and joint fluids of RA patients was significantly higher than that in sera and joint fluids of OA patients. A correlation between serum DcR3 concentration and disease activity was not observed, but the serum DcR3 concentration was strongly correlated with the TNFalpha concentration. DcR3 was highly expressed in serum and joint fluids of RA patients.Modern Rheumatology 10/2009; 20(1):63-8. · 1.58 Impact Factor
