Inhibition of NUCB2 suppresses the proliferation, migration, and invasion of rheumatoid arthritis synovial fibroblasts from patients with rheumatoid arthritis in vitro

Journal of Orthopaedic Surgery and Research

Research Article

Genxiang Rong¹  Shuo Zhang²  Juehua Jing²  Tao Zhang³  Yayun Xu⁴ 

[1] Department of Orthopedics, The First Affiliated Hospital of Anhui Medical University, Hefei, China;Department of Orthopedics, The Second Affiliated Hospital of Anhui Medical University, 678 Furong Road, 230032, Hefei, Anhui, People’s Republic of China;Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China;Inflammation and Immune Mediated Diseases Laboratory of Anhui Province, School of Pharmacy, Anhui Medical University, Hefei, China;Department of Epidemiology and Biostatistics, School of Public Health, Anhui Medical University, Hefei, China;

关键词: Rheumatoid arthritis;    Synovial fibroblast;    Nucleobindin-2;    Synovium;    Proliferation;    Migration;    Invasion;   

DOI  :  10.1186/s13018-022-03453-2

 received in 2022-05-30, accepted in 2022-12-15,  发布年份 2022

来源: Springer

【 摘 要 】

Rheumatoid arthritis (RA) is an autoimmune polyarthritis in which synovial fibroblasts (SF) play a major role in cartilage and bone destruction through tumorlike proliferation, migration, and invasion. Nesfatin-1, an 82-amino-acid-long peptide discovered by Oh-I in 2006, is derived from the precursor protein nucleobindin-2 (NUCB2). NUCB2/nesfatin-1 promotes cell proliferation, migration, and invasion in various tumors. We have previously shown that increased nesfatin-1 levels in the synovium may be associated with disease severity in patients with RA. However, the effect of NUCB2 on the tumorlike transformation of RASF has not yet been reported. The expression of NUCB2 mRNA in the synovium of RA and non-RA patients was further confirmed using three individual datasets from the NCBI GEO database. Gene set enrichment analysis (GSEA) was employed to explore the association between NUCB2 mRNA and RA-related gene signatures or signaling pathways in the GSE77298 dataset. Cell proliferation, migration, and invasion abilities were determined using Cell Counting Kit-8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU), wound healing, and transwell assays, respectively. The results showed that the levels of NUCB2 mRNA in the synovium were significantly elevated in patients with RA. Moreover, GSEA showed that high expression of NUCB2 mRNA was related to gene signatures, including those involved in the cell cycle, DNA replication, extracellular matrix–receptor interaction, and focal adhesion. Furthermore, the results of CCK-8 and EdU assays indicated that inhibition of NUCB2 markedly repressed RASF proliferation. Additionally, the results of wound healing and transwell assays demonstrated that inhibition of NUCB2 significantly suppressed the migratory and invasive abilities of RASFs. Our findings are the first to demonstrate that the inhibition of NUCB2 suppresses the proliferation, migration, and invasion of RASFs in vitro.

【 授权许可】

CC BY   
© The Author(s) 2022

【 图 表 】

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