Possible chondroprotective effect of canakinumab: An in vitro study on human osteoarthritic chondrocytes

Canakinumab is a human IgGκ monoclonal antibody that neutralizes the activity of interleukin (IL)-1β blocking interaction with IL-1β receptors. Our study aimed to evaluate the in vitro effect of canakinumab on human osteoarthritic (OA) chondrocytes cultivated in the presence or absence of tumor necrosis factor (TNF)-α. Articular cartilage was obtained from the femoral heads of patients with osteoarthritis (OA). Chondrocytes were incubated with two concentrations (1 μg/ml and 10 μg/ml) of canakinumab alone or with TNF-α (10 ng/ml) for 48 h. We evaluated cell viability, release of proteoglycans (PG) and nitric oxide (NO) in culture medium, inducible nitric oxide synthase (iNOS) and metalloproteinanes (MMP)-1,3,13 gene expression, apoptosis, necrosis and morphological feature by transmission electron microscopy (TEM). Canakinumab alone did not have cytotoxic effect. Cell viability was reduced significantly (p < 0.001) by TNF-α and restored by canakinumab at both concentrations used. TNF-α determined a significant decrease of PG (p < 0.001) and an increase of NO (p < 0.001) and MMP-1,3,13 gene expression. Canakinumab significantly increased the PG levels and decreased (1 μg/ml, p < 0.01; 10 μg/ml, p < 0.01) NO levels in cells cultured with TNF-α. The NO data were confirmed by the immunocytochemistry assay for iNOS. A significant reduction of MMP-1,3,13 gene expression was induced by canakinumab. Our experiments confirmed the pro-apoptotic effect of TNF-α and demonstrated a protective role of canakinumab. The results concerning biochemical data were further confirmed by the morphological findings obtained by TEM. We showed that canakinumab counteracts the negative effects of TNF-α on OA chondrocyte cultures and may have a potential chondroprotective role in OA.