Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis

Autor: MA Nielsen, D Køster, S Greisen, A Troldborg, K Stengaard-Pedersen, P Junker, K Hørslev-Petersen, ML Hetland, M Østergaard, M Hvid, H Leffler, TW Kragstrup, B Deleuran
Rok vydání: 2022
Předmět:
Zdroj: Nielsen, M A, Køster, D, Greisen, S, Troldborg, A, Stengaard-Pedersen, K, Junker, P, Hørslev-Petersen, K, Hetland, M L, Østergaard, M, Hvid, M, Leffler, H, Kragstrup, T W & Deleuran, B 2023, ' Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis ', Scandinavian Journal of Rheumatology, vol. 52, no. 1, pp. 33-41 . https://doi.org/10.1080/03009742.2021.1992860
Nielsen, M A, Køster, D, Greisen, S, Troldborg, A, Stengaard-Pedersen, K, Junker, P, Hørslev-Petersen, K, Hetland, M L, Østergaard, M, Hvid, M, Leffler, H, Kragstrup, T W & Deleuran, B 2022, ' Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis ', Scandinavian Journal of Rheumatology . https://doi.org/10.1080/03009742.2021.1992860
DOI: 10.6084/m9.figshare.18319284
Popis: OBJECTIVE: Galectin-3 (Gal-3) has been suggested as a proinflammatory mediator in rheumatoid arthritis (RA). We aimed to study clinical and pathogenic aspects of Gal-3 in RA.METHOD: Plasma samples from healthy controls (n = 48) and patients with newly diagnosed, early RA were assayed for soluble Gal-3. In patients with chronic RA (n = 18), Gal-3 was measured in both plasma and synovial fluid. Synovial fluid mononuclear cells were used to purify fibroblast-like synoviocytes (FLSs) and osteoclasts. Monocultures of FLSs and autologous co-cultures of FLSs and peripheral blood mononuclear cells were established and co-incubated with a Gal-3 inhibitor.RESULTS: Patients with early and chronic RA had persistently increased plasma levels of Gal-3 compared with controls. However, changes in plasma Gal-3 at the level of individuals were associated with long-term disease activity. In seropositive early RA patients, all patients with decreasing plasma Gal-3 from 0 to 3 months had low disease activity after 2 years (p < 0.05). Gal-3 levels in synovial fluid were markedly elevated. In vitro, co-incubation with a Gal-3 inhibitor (GB1107, 10 µM) led to a significant reduction in both interleukin-1β and tumour necrosis factor-α secretion from FLS monocultures (both p < 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p < 0.05).CONCLUSIONS: Our findings underscore the role of Gal-3 regarding disease activity and tissue destruction in RA. An initial decrease in plasma Gal-3 levels predicted decreased long-term disease activity. Correspondingly, a Gal-3 inhibitor decreased the activity of inflammatory FLSs and osteoclastogenesis in patients with RA.
Databáze: OpenAIRE
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