Sulforaphane protects human chondrocytes against cell death induced by various stimuli

Chondrocyte cell death can contribute to cartilage degeneration in articular diseases, such as osteoarthritis (OA). Sulforaphane (SFN), a natural compound derived from cruciferous aliment, is well known as an anti‐carcinogen, but according to recent evidence it also shows cytoprotective effects on a variety of non‐tumoral cells. Therefore we have tested the ability of SFN to protect chondrocytes from cell death in vitro. Treatment of growing monolayer cultures of human C‐28/I2 chondrocytes with SFN in the low micro‐molecular range for a few days, reduced cell growth without affecting cell survival or inducing apoptosis. However it decreased cell death in C‐28/I2 chondrocytes exposed to stimuli previously reported to promptly trigger apoptosis, that is, the cytokine tumor necrosis factor‐α (TNF) plus cycloheximide (CHX) or the polyamine analogue N1,N11‐diethylnorspermine (DENSPM) plus CHX. In particular pre‐treatment with SFN reduced effector and initiator caspase activities and the associated activation of JNK kinases. SFN exerted a cytoprotective action even versus H2O2, which differently from the previous stimuli induced cell death without producing an evident caspase activation. SFN pre‐treatment also prevented caspase activation in three‐dimensional micromass cultures of OA chondrocytes stimulated with growth‐related oncogene α (GROα), a pro‐apoptotic chemokine. The suppression of caspase activation in micromasses appeared to be related to the inhibition of p38 MAPK phosphorylation. In conclusion, the present work shows that low micro‐molecular SFN concentrations exert pro‐survival and anti‐apoptotic actions and influence signaling pathways in a variety of experimental conditions employing chondrocyte cell lines and OA chondrocytes treated with a range of death stimuli. J. Cell. Physiol. 226: 1771–1779, 2011. © 2010 Wiley‐Liss, Inc.