論文 - 詳細
| RRC ID | 19280 |
|---|---|
| 著者 | Nozawa K, Fujishiro M, Kawasaki M, Kaneko H, Iwabuchi K, Yanagida M, Suzuki F, Miyazawa K, Takasaki Y, Ogawa H, Takamori K, Sekigawa I. |
| タイトル | Connective tissue growth factor promotes articular damage by increased osteoclastogenesis in patients with rheumatoid arthritis. |
| ジャーナル | Arthritis Res Ther |
| Abstract |
INTRODUCTION:A protein analysis using a mass spectrometry indicated that there are serum proteins showing significant quantitative changes after the administration of infliximab. Among them, connective tissue growth factor (CTGF) seems to be related to the pathogenesis of rheumatoid arthritis (RA). Therefore, this study was conducted to investigate how CTGF is associated with the disease progression of RA. METHODS:Serum samples were collected from RA patients in active or inactive disease stages, and before or after treatments with infliximab. CTGF production was evaluated by ELISA, RT-PCR, indirect immunofluorescence microscopy, and immunoblotting. Osteoclastogenesis was evaluated using tartrate-resistant acid phosphatase (TRAP) staining, a bone resorption assay and osteoclasts specific catalytic enzymes productions. RESULTS:The serum concentrations of CTGF in RA were greater than in normal healthy controls and disease controls. Interestingly, those were significantly higher in active RA patients compared to inactive RA patients. Furthermore, the CTGF levels significantly were decreased by infliximab concomitant with the disease amelioration. In addition, tumour necrosis factor (TNF)alpha can induce the CTGF production from synovial fibroblasts even though TNFalpha can oppositely inhibit the production of CTGF from chondrocytes. CTGF promoted the induction of the quantitative and qualitative activities of osteoclasts in combination with M-CSF and receptor activator of NF-kappaB ligand (RANKL). In addition, we newly found integrin alphaVbeta3 on the osteoclasts as a CTGF receptor. CONCLUSIONS:These results indicate that aberrant CTGF production induced by TNFalpha plays a central role for the abnormal osteoclastic activation in RA patients. Restoration of aberrant CTGF production may contribute to the inhibition of articular destruction in infliximab treatment. |
| 巻・号 | 11(6) |
| ページ | R174 |
| 公開日 | 2009-1-1 |
| DOI | 10.1186/ar2863 |
| PII | ar2863 |
| PMID | 19922639 |
| PMC | PMC3003536 |
| MeSH | Antibodies, Monoclonal / therapeutic use Antirheumatic Agents / therapeutic use Arthritis, Rheumatoid / drug therapy Arthritis, Rheumatoid / metabolism* Arthritis, Rheumatoid / pathology Blotting, Western Cell Differentiation / physiology Connective Tissue Growth Factor / metabolism* Disease Progression Enzyme-Linked Immunosorbent Assay Fluorescent Antibody Technique Humans Immunohistochemistry Immunoprecipitation Infliximab Osteoclasts / cytology Osteoclasts / metabolism* Reverse Transcriptase Polymerase Chain Reaction Tumor Necrosis Factor-alpha / metabolism |
| IF | 4.103 |
| 引用数 | 41 |
| WOS 分野 | RHEUMATOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | MH7A(RCB1512) |