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Blockade of translationally controlled tumor protein attenuated the aggressiveness of fibroblast-like synoviocytes and ameliorated collagen-induced arthritis.
- Source :
-
Experimental & molecular medicine [Exp Mol Med] 2021 Jan; Vol. 53 (1), pp. 67-80. Date of Electronic Publication: 2021 Jan 06. - Publication Year :
- 2021
-
Abstract
- Histamine releasing factor/translationally controlled tumor protein (HRF/TCTP) stimulates cancer progression and allergic responses, but the role of HRF/TCTP in rheumatoid arthritis (RA) remains undefined. In this study, we explored the pathogenic significance of HRF/TCTP and evaluated the therapeutic effects of HRF/TCTP blockade in RA. HRF/TCTP transgenic (TG) and knockdown (KD) mice with collagen-induced arthritis (CIA) were used to determine the experimental phenotypes of RA. HRF/TCTP levels in the sera of RA patients were measured and compared to those from patients with osteoarthritis (OA), ankylosing spondylitis, Behçet's disease, and healthy controls. HRF/TCTP expression was also assessed in the synovium and fibroblast-like synoviocytes (FLSs) obtained from RA or OA patients. Finally, we assessed the effects of HRF/TCTP and dimerized HRF/TCTP-binding peptide-2 (dTBP2), an HRF/TCTP inhibitor, in RA-FLSs and CIA mice. Our clinical, radiological, histological, and biochemical analyses indicate that inflammatory responses and joint destruction were increased in HRF/TCTP TG mice and decreased in KD mice compared to wild-type littermates. HRF/TCTP levels in the sera, synovial fluid, synovium, and FLSs were higher in patients with RA than in control groups. Serum levels of HRF/TCTP correlated well with RA disease activity. The tumor-like aggressiveness of RA-FLSs was exacerbated by HRF/TCTP stimulation and ameliorated by dTBP2 treatment. dTBP2 exerted protective and therapeutic effects in CIA mice and had no detrimental effects in a murine tuberculosis model. Our results indicate that HRF/TCTP is a novel biomarker and therapeutic target for the diagnosis and treatment of RA.
- Subjects :
- Animals
Anti-Inflammatory Agents pharmacology
Anti-Inflammatory Agents therapeutic use
Arthritis, Experimental drug therapy
Arthritis, Rheumatoid drug therapy
Cells, Cultured
Humans
Mice
Mice, Inbred C57BL
Oligopeptides pharmacology
Oligopeptides therapeutic use
Protein Binding
Tumor Protein, Translationally-Controlled 1 antagonists & inhibitors
Tumor Protein, Translationally-Controlled 1 genetics
Arthritis, Experimental metabolism
Arthritis, Rheumatoid metabolism
Fibroblasts metabolism
Synoviocytes metabolism
Tumor Protein, Translationally-Controlled 1 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 2092-6413
- Volume :
- 53
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Experimental & molecular medicine
- Publication Type :
- Academic Journal
- Accession number :
- 33408335
- Full Text :
- https://doi.org/10.1038/s12276-020-00546-y