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SAT0569 Galectin 3 Exerts A Protective Role in A Murine Model of Osteoarthritis
  1. N. Hafsia1,
  2. F. Poirier2,
  3. D. Delacour2,
  4. P. Reboul3,
  5. D. Côme4,
  6. P. Van Lent5,
  7. M. Cohen-Solal6,
  8. F. Lioté6,
  9. H.K. Ea6
  1. 1INSERM U 1132, Paris 7 Diderot University, Lariboisière Hospital, APHP
  2. 2Morphogenesis, Homeostasis and Pathologies, UMR 7592 CNRS Institut Jacques Monod, Paris
  3. 3Imagerie Moléculaire et Physiopathologie Articulaire (IMoPA), UMR 7365 CNRS, BioPole de l'Université de Lorraine, Vandoeuvre-lès-Nancy
  4. 4Anatomy Pathology, Saint-Anne Hospital, Paris, France
  5. 5Rheumatology, UMCN/NCMLS, Nijmegen, Netherlands
  6. 6Rheumatology, INSERM U 1132, Paris 7 Diderot University, Lariboisière Hospital, AP-HP, Paris, France


Background Osteoarthritis (OA) is the most common adult joint disease characterized by cartilage destruction, subchondral bone remodelling and mild synovial inflammation. Pathogenesis of OA involves overload, ageing, genetic factors and chondrocyte dysregulation. Galectin 3 (Gal3) expression is increased in OA cartilage and synovial fluid. Gal3 is involved in multiple cellular functions including proliferation, differentiation and cell death. During embryogenesis, the growth plate of Gal3 mutant mice has a reduction of hypertrophic zone and many lacunae due to a loss of chondrocytes. These results suggest a role of Gal3 in chondrocyte dedifferentiation.

Objectives To determine the role of Gal3 in osteoarthritis and to assess its functions in chondrocyte biology.

Methods In vivo, murine OA was induced in Wild type (WT) 129 and Gal3 mutant mice by partial medial meniscectomy (MNX) of the right knee. A sham operation was performed on the left knee. Animals were sacrificed 4 weeks after surgery. Cartilages lesions were assessed according to OARSI recommendations. Chondrocyte apoptosis was assessed by TUNEL labelling and chondrocyte catabolism by immunostaining for aggrecanases and metalloproteases. Subchondral bone modifications were evaluated by microCT.

In vitro, primary murine chondrocytes, isolated from new born WT and Gal3 mutant mice, were cultured and stimulated by inflammatory cytokines (IL-1β and TNF-α). Anabolism, catabolic and differentiation responses were assessed by RT-qPCR

Results In vivo, MNX induced in Gal3 mutant mice more severe OA cartilage lesions compared to WT as assessed by OARSI scoring (4.4±1.0 vs 1.3±0.8, p<0.05). Expression of Gal3 decreased in WT cartilages after MNX compared to sham operated cartilage (34.5% ±4.9 vs 53.0% ±2.8; p<0.01). Cartilages lesions were associated with higher ratio of chondrocyte positive-TUNEL staining in Gal3 mutant cartilages compared to WT (17.7% ±6.2 vs 10.6% ±3.3 p<0.02). Similarly, immunostaining for ADAMTS-5 (26.7% ±0.5 vs 16.0% ±1.4, p<0.02) and VDIPEN (52.0% ±4.0 vs 30.0% ±2.0, p<0.05) was increased in Gal3 mutant cartilages. Moreover, collagen type X expression was increased in Gal3 mutant cartilage. No difference was observed in subchondral bone modifications. In vitro, IL-1β stimulation increased ADAMTS-4 (4.6±2.0 vs; 1.6±0.3, p<0.05) and ADAMTS-5 (4.5±2.2 vs 1.8±1.0, p<0.05) mRNA expressions in Gal3 mutant chondrocytes compared to WT chondrocytes.

Conclusions Gal3 deletion exacerbated murine OA lesions induced by mechanical stress. OA lesions were associated with increased chondrocyte catabolism, differentiation and death. These results suggested Gal3 had a protective role in OA and chondrocyte homeostasis.

Disclosure of Interest None declared

DOI 10.1136/annrheumdis-2014-eular.4750

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