Open Access Highly Accessed Research article

Extracellular localization of galectin-3 has a deleterious role in joint tissues

Audrée Janelle-Montcalm1, Christelle Boileau1, Françoise Poirier2, Jean-Pierre Pelletier1, Mélanie Guévremont1, Nicolas Duval3, Johanne Martel-Pelletier1 and Pascal Reboul1*

Author Affiliations

1 Unité de Recherche en Arthrose, Centre de Recherche de l'Université de Montréal (CRCHUM), Montréal, Québec, H2L 4M1, Canada

2 Universités Paris 6 et Paris 7, Institut Jacques Monod, CNRS UMR 7592, Place Jussieu, 75251 Paris Cedex 05, France

3 Pavillon des Charmilles, boulevard des Laurentides, Vimont, Québec H7M 2Y3, Canada

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Arthritis Research & Therapy 2007, 9:R20  doi:10.1186/ar2130

Published: 27 February 2007


In this study we examine the extracellular role of galectin-3 (gal-3) in joint tissues. Following intra-articular injection of gal-3 or vehicle in knee joints of mice, histological evaluation of articular cartilage and subchondral bone was performed. Further studies were then performed using human osteoarthritic (OA) chondrocytes and subchondral bone osteoblasts, in which the effect of gal-3 (0 to 10 μg/ml) was analyzed. Osteoblasts were incubated in the presence of vitamin D3 (50 nM), which is an inducer of osteocalcin, encoded by an osteoblast terminal differentiation gene. Genes of interest mainly expressed in either chondrocytes or osteoblasts were analyzed with real-time RT-PCR and enzyme immunoassays. Signalling pathways regulating osteocalcin were analyzed in the presence of gal-3. Intra-articular injection of gal-3 induced knee swelling and lesions in both cartilage and subchondral bone. On human OA chondrocytes, gal-3 at 1 μg/ml stimulated ADAMTS-5 expression in chondrocytes and, at higher concentrations (5 and 10 μg/ml), matrix metalloproteinase-3 expression. Experiments performed with osteoblasts showed a weak but bipolar effect on alkaline phosphatase expression: stimulation at 1 μg/ml or inhibition at 10 μg/ml. In the absence of vitamin D3, type I collagen alpha 1 chain expression was inhibited by 10 μg/ml of gal-3. The vitamin D3induced osteocalcin was strongly inhibited in a dose-dependent manner in the presence of gal-3, at both the mRNA and protein levels. This inhibition was mainly mediated by phosphatidylinositol-3-kinase. These findings indicate that high levels of extracellular gal-3, which could be encountered locally during the inflammatory process, have deleterious effects in both cartilage and subchondral bone tissues.