Intracellular localisation of galectin-3 has a protective role in chondrocyte survival

Objective: Although galectin-3 (gal-3) is expressed during arthritic disorders, the part it plays has never been described. The aim of the study was to determine the intracellular roles of gal-3 in chondrocytes and cartilage. Methods: Following treatment with sodium nitroprusside, a cell death inducer, intracellular levels of total and phosphorylated gal-3 were measured by immunoblots in human osteoarthritic (OA) chondrocytes. Cell viability was also assessed by the lactate dehydrogenase activity in conditioned media from OA chondrocytes or from ATDC5 cells transfected with a gal-3-expressing vector. After generating an OA model by intra-articular injection of 0.5% mono-iodoacetate (MIA), histological evaluation of articular cartilage and subchondral bone was performed in wild-type (WT) and gal-3 knockout (KO) mice aged 6 weeks and 4 months. Results: In vitro experiments demonstrated that intracellular gal-3 had a protective role in chondrocyte survival, which involved its phosphorylation. In contrast to 6-week-old mice, 4-month-old gal-3 KO mice, compared with WT mice, presented OA-like cartilage modifications. OA induction via MIA injection in WT mice generated cartilage lesions similar to those found in gal-3 KO animals. Moreover, OA induction showed a significant decrease in subchondral bone surface in the gal-3 KO mice in contrast to the WT group. Conclusions: Altogether these findings indicate that intracellular gal-3 has a beneficial effect in articular cells, as its absence in KO mice led to cartilage lesions.