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

Nielsen, M. A. ; Køster, D. ; Greisen, S. ; Troldborg, A. ; Stengaard-Pedersen, K. ; Junker, P. ; Hørslev-Petersen, K. ; Hetland, M. L. ; Østergaard, M. and Hvid, M. , et al. (2023) In Scandinavian Journal of Rheumatology 52(1). p.33-41
Abstract

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... (More)

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.

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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Scandinavian Journal of Rheumatology
volume
52
issue
1
pages
33 - 41
publisher
Taylor & Francis
external identifiers
  • scopus:85122873255
  • pmid:35023445
ISSN
0300-9742
DOI
10.1080/03009742.2021.1992860
language
English
LU publication?
yes
id
2ffa4ec8-f56f-4df6-9bac-e9986f40a856
date added to LUP
2022-02-24 15:05:39
date last changed
2024-06-15 19:39:06
@article{2ffa4ec8-f56f-4df6-9bac-e9986f40a856,
  abstract     = {{<p>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 &lt; 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 &lt; 0.05) and decreased monocyte-derived osteoclastogenesis compared with controls (both p &lt; 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.</p>}},
  author       = {{Nielsen, M. A. and Køster, D. and Greisen, S. and Troldborg, A. and Stengaard-Pedersen, K. and Junker, P. and Hørslev-Petersen, K. and Hetland, M. L. and Østergaard, M. and Hvid, M. and Leffler, H. and Kragstrup, T. W. and Deleuran, B.}},
  issn         = {{0300-9742}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{33--41}},
  publisher    = {{Taylor & Francis}},
  series       = {{Scandinavian Journal of Rheumatology}},
  title        = {{Increased synovial galectin-3 induce inflammatory fibroblast activation and osteoclastogenesis in patients with rheumatoid arthritis}},
  url          = {{http://dx.doi.org/10.1080/03009742.2021.1992860}},
  doi          = {{10.1080/03009742.2021.1992860}},
  volume       = {{52}},
  year         = {{2023}},
}