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

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  • M A Nielsen
  • D Køster, Aarhus University
  • ,
  • S Greisen
  • ,
  • A Troldborg
  • K Stengaard-Pedersen
  • P Junker, Department of Rheumatology, Odense University Hospital, Odense, Denmark Danbio National Registry, Glostrup University Hospital, Denmark.
  • ,
  • K Hørslev-Petersen, University of Southern Denmark
  • ,
  • M L Hetland, Copenhagen Center for Arthritis Research (COPECARE)
  • ,
  • M Østergaard, Copenhagen Center for Arthritis Research (COPECARE)
  • ,
  • M Hvid
  • H Leffler, Department of Clinical Sciences, Lund University, Skane University Hospital, Lund, Sweden; Department of Cardiothoracic Surgery, Lund University, Skåne University Hospital, Lund, Sweden.
  • ,
  • T W Kragstrup
  • B Deleuran

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.

Original languageEnglish
JournalScandinavian Journal of Rheumatology
Pages (from-to)1-9
Number of pages9
ISSN0300-9742
DOIs
Publication statusE-pub ahead of print - 13 Jan 2022

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