MicroRNA-27a-3p enhances the inflammatory phenotype of Juvenile Idiopathic Arthritis fibroblast-like synoviocytes

• Main Authors: Claire H. Bullock (Author), Sarah M. McAlpine (Author), Sarah E. Roberts (Author), Beata Derfalvi (Author)
• Format: Book
• Published: BMC, 2023-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.1186/s12969-023-00833-8; 1546-0096
• Keywords: Fibroblast-like synoviocytes; Inflammation; Juvenile idiopathic arthritis; microRNA; Synovial fluid; Pediatrics; RJ1-570; Diseases of the musculoskeletal system; RC925-935
• Source: Pediatric Rheumatology Online Journal, Vol 21, Iss 1, Pp 1-12 (2023)

Abstract Background Juvenile Idiopathic Arthritis (JIA) is the most prevalent chronic pediatric rheumatic disorder. In joints of JIA patients, aggressive phenotypic changes in fibroblast-like synoviocytes (FLS) of the synovial lining play a key role in inflammation. MicroRNAs are dysregulated in rheumatoid arthritis and JIA, including miR-27a-3p. However, it is not understood if miR-27a-3p, enriched in JIA synovial fluid (SF) and leukocytes, alters FLS function. Methods Primary JIA FLS cells were transfected with a miR-27a-3p mimic or a negative control microRNA (miR-NC) and stimulated with pooled JIA SF or inflammatory cytokines. Viability and apoptosis were analyzed by flow cytometry. Proliferation was evaluated using a 3H-thymidine incorporation assay. Cytokine production was assessed by qPCR and ELISA. Expression of TGF-β pathway genes was determined using a qPCR array. Results MiR-27a-3p was constitutively expressed in FLS. Overexpression of miR-27a-3p caused increased interleukin-8 secretion in resting FLS, and interleukin-6 was elevated in SF-activated FLS compared to miR-NC. Furthermore, stimulation with pro-inflammatory cytokines augmented FLS proliferation in miR-27a-3p-transfected FLS relative to miR-NC. Expression of multiple TGF-β pathway genes was modulated by overexpression of miR-27a-3p. Conclusions MiR-27a-3p significantly contributes to FLS proliferation and cytokine production, making it a potential candidate for epigenetic therapy that targets FLS in arthritis.