Are FoxO transcription factors implicated in osteoarthritis? Influence of Diacerhein.

ABSTRACT

The FoxO family of Forkhead transcription factors functions at the interface of tumor suppression, energy metabolism and organismal longevity. FoxO factors are key downstream targets of insulin, growth factor, nutrient and oxidative stress stimuli that coordinate a wide-range of cellular outputs. These transcription factors could participate in the regulation of different phenomena found in the osteoarthritis pathology, like apoptosis, chondrocyte proliferation, cell dedifferentiation or resistance to oxidative stress. Moreover, we found recently that FoxO transcription factors could be involved on Diacerhein mode of action, a drug that reduces the IL-1ß deleterious effects on osteoarthritis cartilage through inhibition of the expression of degrading enzymes. It could explain the downregulated proliferation and the increased p27 expression observed on human osteoarthritic chondrocytes in the presence of Diacerhein.