Phospholipase C-eta2, As a C2 Domain-Containing Protein, Regulate Aggressiveness of Fibroblast‐like Synoviocytes and Ameliorate Arthritis in Experimental Animal Models of Rheumatoid Arthritis

Mingyo Kim, Hyun Min Jeon, Hae Sook Noh, Sang Mi Yi and Sang-Il Lee, Department of Internal Medicine and Institute of Health Science, Gyeongsang National University School of Medicine, Jinju, Korea, Republic of (South)

Meeting: 2018 ACR/ARHP Annual Meeting

Keywords: Animal models, phospholipase, rheumatoid arthritis, synovial fluid, synovium and synovial cells

Session Information

Date: Monday, October 22, 2018

Title: Rheumatoid Arthritis – Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: The C2 domain is a Ca²⁺-dependent membrane-targeting motif found in many cellular proteins involved in signal transduction or inflammatory pathway. However, the effects of C2 domain-containing proteins in the pathogenesis of rheumatoid arthritis (RA) have not yet been elucidated. This study aims at screening the novel C2 domain-containing proteins related to the aggressiveness of RA fibroblast-like synoviocyte (RA-FLS) and confirm its precise roles in RA.

Methods: A recombinant adenovirus library expressing 145 kinds of C2 domains was transduced into RA-FLS to check the effects on the proliferation and NF-kB activation. Phospholipase C-eta2 (PLCH2) was selected as a target for C2 domain-containing protein. Recombinant adenovirus expressing PLCH2 (Adv-PLCH2) or C2 domain of PLCH2 (Adv-PLCH2_C2) were used for in vitro experiments using RA-FLS and MH7A cell line. The effect on the cell death of PLCH2 was assessed in vivo using a mouse Matrigel-plug model. Collagen-induced arthritis (CIA) model is also used to investigate the anti-arthritic effects of Adv-PLCH2, Adv-PLCH2_C2, and m-3M3FBS (PLC activator).

Results: PLCH2 levels were decreased in the RA-synovium and RA-FLS compared to osteoarthritis (OA), and further reduced after stimulation of LPS. Adv-PLCH2 and Adv-PLCH2_C2 suppressed proliferation, migration, invasion, NF-κB activation, cytokines/proteases production of RA-FLS and MH7A cell line. Adv-PLCH2 and Adv-PLCH2_C2 sensitized RA-FLS to apoptosis in vitro and in vivo model. Adv-PLCH2 or Adv-PLCH2_C2, as an intra-articular delivery, and m-3M3FBS, as systemic delivery of PLC activator, ameliorated inflammation and bone destruction in CIA mice.

Conclusion: Our data identify that PLCH2 and its activation efficiently suppress the aggressiveness of RA-FLS and inflammatory arthritis of CIA and suggest that PLCH2 may be an intriguing therapeutic target in RA.

Disclosure: M. Kim, None; H. M. Jeon, None; H. S. Noh, None; S. M. Yi, None; S. I. Lee, None.

To cite this abstract in AMA style:

Kim M, Jeon HM, Noh HS, Yi SM, Lee SI. Phospholipase C-eta2, As a C2 Domain-Containing Protein, Regulate Aggressiveness of Fibroblast‐like Synoviocytes and Ameliorate Arthritis in Experimental Animal Models of Rheumatoid Arthritis [abstract]. Arthritis Rheumatol. 2018; 70 (suppl 9). https://acrabstracts.org/abstract/phospholipase-c-eta2-as-a-c2-domain-containing-protein-regulate-aggressiveness-of-fibroblast%e2%80%90like-synoviocytes-and-ameliorate-arthritis-in-experimental-animal-models-of-rheumatoid-arthritis/. Accessed .

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