Wanvisa UdomsinprasertArtit JinawathNipaporn TeerawattanapongSittisak HonsawekChulalongkorn UniversityFaculty of Medicine, Ramathibodi Hospital, Mahidol UniversityMahidol UniversityFaculty of Medicine, Siriraj Hospital, Mahidol University2020-06-022020-06-022020-12-01Scientific Reports. Vol.10, No.1 (2020)204523222-s2.0-85084704762https://repository.li.mahidol.ac.th/handle/20.500.14594/56358© 2020, The Author(s). This study aimed to investigate whether interleukin-34 (IL-34) mRNA expression is aberrant and modulated by tumor necrosis factor-alpha (TNF-α) in knee osteoarthritis (OA) fibroblast-like synoviocytes (FLS) and determine associations of IL-34 mRNA and protein in the systemic and local joint environments with severity of knee OA synovitis. Transcriptional and translational IL-34 levels in FLS, synovium, synovial fluid, and plasma of knee OA were determined using real-time polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay. Relative mRNA expressions of NF-κB signaling molecules were further measured. In knee OA FLS stimulated with TNF-α, IL-34 mRNA expression was significantly up-regulated in a time-dependent manner. In knee OA synovium with severe synovitis, increased IL-34 mRNA expression was directly associated with IL-6, IκB, NF-κB, and MMP-13, in addition to knee OA FLS. Immunostaining score of IL-34 was considerably greater in knee OA synovium with severe synovitis than that in those with mild and no synovitis. Increments in joint fluid and plasma IL-34 levels in knee OA patients with severe synovitis were closely related to its mRNA and protein expressions in knee OA synovium. Transcriptional and translational expressions of IL-34 were positively correlated with synovitis severity. Collectively, IL-34 overexpression would reflect synovitis severity in knee OA.Mahidol UniversityMultidisciplinaryInterleukin-34 overexpression mediated through tumor necrosis factor-alpha reflects severity of synovitis in knee osteoarthritisArticleSCOPUS10.1038/s41598-020-64932-2