Extracellular localization of galectin-3 has a deleterious role in joint tissues.
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 microg/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 microg/ml stimulated ADAMTS-5 expression in chondrocytes and, at higher concentrations (5 and 10 microg/ml), matrix metalloproteinase-3 expression. Experiments performed with osteoblasts showed a weak but bipolar effect on alkaline phosphatase expression: stimulation at 1 microg/ml or inhibition at 10 microg/ml. In the absence of vitamin D3, type I collagen alpha 1 chain expression was inhibited by 10 microg/ml of gal-3. The vitamin D3 induced 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.
Janelle-Montcalm
Audrée
A
Unité de Recherche en Arthrose, Centre de Recherche de l'Université de Montréal (CRCHUM), Montréal, Québec, Canada. kawa_akari@yahoo.ca
Boileau
Christelle
C
Poirier
Françoise
F
Pelletier
Jean-Pierre
JP
Guévremont
Mélanie
M
Duval
Nicolas
N
Martel-Pelletier
Johanne
J
Reboul
Pascal
P
D000368:Aged; D000818:Animals; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology; D002358:Cartilage, Articular / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D045604:Extracellular Fluid / Q000737:chemistry* / Q000378:metabolism*; D005260:Female; D037502:Galectin 3 / Q000008:administration & dosage / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D007596:Joints / Q000737:chemistry* / Q000378:metabolism* / Q000473:pathology; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology
D037502:Galectin 3