AB0770 WISP1 PROMOTES THE PROGRESSION OF RHEUMATOID ARTHRITIS THROUGH NLRP3 INFLAMMASOME ACTIVATION
Authors: H. Wang, H. Chen, Z. Tang, K. Xie
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Rheumatoid arthritis (RA) is a chronic autoimmune disease without effective treatments. This study explored WNT1 inducible signaling pathway protein 1 (WISP1) as a potential target to prevent RA. <h3>Objectives:</h3> This study explored WNT 1 inducible signaling pathway protein 1 (WISP 1) as a potential target to prevent RA. <h3>Methods:</h3> Ad-shRNA-WISP1 or NC vector was injected in each ankle of collagen-induced arthritis (CIA) rats. Si-WISP1 or NC vector was transfected to TNF-α-induced fibroblast-like synoviocytes (FLSs). The effects of WISP1 knockdown on levels of pro-inflammatory factors in rats or FLSs were examined by RT-qPCR, ELISA, or western blot. CCK-8, EdU, wound-healing, transwell assays were used to estimate the effects of WISP1 knockdown on TNF-α-induced proliferation, migration, and invasion in FLSs. The NLRP3 inflammasome-related proteins were checked by immunohistochemistry, immunofluorescence assay, or western blot in rats or FLSs. <h3>Results:</h3> Administration of WISP1 knockdown declined arthritis scores, alleviated joint damage, and reduced synovial inflammation in CIA rats. WISP1 knockdown restrained TNF-α-induced proliferation, migration, and invasion in FLSs. In CIA rats and TNFα-induced FLSs, WISP1 knockdown reduced the secretion of inflammatory factors and restrained NLRP3 inflammasome activation. <h3>Conclusion:</h3> WISP1 knockdown effectively inhibited NLRP3 inflammasome activation and inflammatory factors levels, and bringing a candidate target for treatment of RA. <h3>REFERENCES:</h3> [1] SMOLEN JS, ALETAHA D, MCINNES IB. Rheumatoid arthritis [J]. Lancet. 2016,388(10055):2023-38. [2] HUNTER TM, BOYTSOV NN, ZHANG X, SCHROEDER K, MICHAUD K, ARAUJO AB. Prevalence of rheumatoid arthritis in the United States adult population in healthcare claims databases, 2004-2014 [J]. Rheumatol Int. 2017,37(9):1551-57. [3] EDILOVA MI, AKRAM A, ABDUL-SATER AA. Innate immunity drives pathogenesis of rheumatoid arthritis [J]. Biomed J. 2021,44(2):172-82. [4] MCINNES IB, BUCKLEY CD, ISAACS JD. Cytokines in rheumatoid arthritis - shaping the immunological landscape [J]. Nat Rev Rheumatol. 2016,12(1):63-8. [5] PALLIO G, MANNINO F, IRRERA N, EID AH, SQUADRITO F. Polymorphisms Involved in Response to Biological Agents Used in Rheumatoid Arthritis [J]. 2020,10(9). [6] MIRR M, OWECKI M. An Update to the WISP-1/CCN4 Role in Obesity, Insulin Resistance and Diabetes [J]. 2021,57(2). [7] MACDONALD IJ, HUANG CC. Targeting CCN Proteins in Rheumatoid Arthritis and Osteoarthritis [J]. 2021,22(9). [8] BARCHETTA I, CIMINI FA, CAPOCCIA D, DE GIOANNIS R, PORZIA A, MAINIERO F, DI MARTINO M, BERTOCCINI L, DE BERNARDINIS M, LEONETTI F, BARONI MG, LENZI A, CAVALLO MG. WISP1 Is a Marker of Systemic and Adipose Tissue Inflammation in Dysmetabolic Subjects With or Without Type 2 Diabetes [J]. J Endocr Soc. 2017,1(6):660-70. [9] VAN DEN BOSCH MH, BLOM AB, KRAM V, MAEDA A, SIKKA S, GABET Y, KILTS TM, VAN DEN BERG WB, VAN LENT PL, VAN DER KRAAN PM, YOUNG MF. WISP1/CCN4 aggravates cartilage degeneration in experimental osteoarthritis [J]. Osteoarthritis Cartilage. 2017,25(11):1900-11. [10] ZHANG M, MENG QC, YANG XF, MU WD. TGF-β1/WISP1/Integrin-α interaction mediates human chondrocytes dedifferentiation [J]. Eur Rev Med Pharmacol Sci. 2020,24(17):8675-84. [11] VAN DEN BOSCH MH, BLOM AB, VAN LENT PL, VAN BEUNINGEN HM, BLANEY DAVIDSON EN, VAN DER KRAAN PM, VAN DEN BERG WB. Canonical Wnt signaling skews TGF-β signaling in chondrocytes towards signaling via ALK1 and Smad 1/5/8 [J]. Cell Signal. 2014,26(5):951-8. [12] KELLEY N, JELTEMA D, DUAN Y, HE Y. The NLRP3 Inflammasome: An Overview of Mechanisms of Activation and Regulation [J]. Int J Mol Sci. 2019,20(13). [13] YIN H, LIU N, SIGDEL KR, DUAN L. Role of NLRP3 Inflammasome in Rheumatoid Arthritis [J]. Front Immunol. 2022,13:931690. <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> <b>None declared.</b>