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02.23 Translationally controlled tumour protein is a critical therapeutic target for rheumatoid arthritis
  1. Sang-Il Lee1,
  2. Min-Gyu Jeon1,
  3. Jung-Yoon Choe2,
  4. Jinseok Kim3,
  5. Heewon Lee4,
  6. Kyunglim Lee4
  1. 1Division of Rheumatology, Department of Internal Medicine, Gyeongsang National University School of Medicine, South Korea
  2. 2Division of Rheumatology, Department of Internal Medicine, Catholic University of Daegu School of Medicine, South Korea
  3. 3Department of Internal Medicine, Jeju National University Hospital, South Korea
  4. 4Graduate School of Pharmaceutical Sciences, Ewha Womans University, South Korea

Abstract

Background Rheumatoid arthritis (RA) is an invasive inflammatory disease leading to severe joint destruction. Fibroblast-like synoviocytes of rheumatoid arthritis (RA-FLS) are key players in RA, and have tumor-like characteristics such as abnormal proliferation and invasion. Translationally Controlled Tumour Protein (TCTP) has been known as a multifunctional protein in cancer progression and allergic response. However, there has been no study to assess the potential roles of TCTP in RA.

Materials and methods The levels of TCTP were checked in the synovial tissue, serum, and synovial fluid of RA patients.The pathologic roles of TCTP were investigated in RA-FLS and TCTP knockdown (kdTCTP) mice with collagen-induced arthritis (CIA). The preventive and therapeutic effects of inhibitor of TCTP were evaluated in CIA mice on the basis of clinical, radiographic, and pathologic scores.

Results TCTP expression was higher in the synovial tissue, serum, and synovial fluid of RA patients than control groups. Dimerized TCTP (dTCTP), as an active form of TCTP, exhibits pro-inflammatory cytokine-like activity, thus dTCTP induced cell proliferation, cytokine secretion, migration, and invasion of RA-FLS. Based on these in vitro observations, in vivo experiment using CIA was performed in kdTCTP and wild type (WT) mice. The results showed that inflammatory response and bone destruction were significantly decreased in kdTCTP mice than WT by investigating clinical score, micro-CT, histological, and biochemical analysis. Finally, we confirmed that dTBP2, as an inhibitor of dTCTP, suppressed tumor-like characteristics of RA-FLS, and had protective and therapeutic effects in CIA mice.

Conclusions Collectively, we suggest that TCTP is a critical therapeutic target and the use of dTBP2 may be a beneficial strategy for the RA treatment.

Keywords
  • Rheumatoid Arthritis
  • Fibroblast-like Synoviocytes
  • Translationally Controlled Tumour Protein

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