Cordycepin protected against the TNF--induced inhibition of osteogenic differentiation of human adipose-derived mesenchymal stem cells

Cordycepin, 3'-deoxyadenosine, is an effective component isolated from the rare Chinese caterpillar fungus Cordyceps militaris. It exerts potent anti-inflammatory actions in different cell and animal models. However, its action remains unclear on the TNF--induced inhibition of osteogenic differentiation of adipose-derived mesenchymal stem cells (ADMSCs). In the present study, we demonstrated that cordycepin induced cell death at 20 and 40 g/mL. Interestingly, 10 g/mL cordycepin abrogated the cell death induced by 20 ng/mL TNF-. Meanwhile, cordycepin exhibited a dose-dependent regulation of the osteogenesis of human ADMSCs: it promoted the differentiation at 10 g/mL, whereas inhibited differentiation at 40 g/mL. Furthermore, we discovered that 10 g/mL cordycepin protected against the TNF- (induced inhibition of osteogenic differentiation of human ADMSCs. It was also revealed that 10 g/mL cordycepin restored Runx2 and Osx mRNA levels, which were significantly inhibited by TNF-during osteogenesis. At the same time, we found that 10 g/mL cordycepin suppressed TNF--activated NF-B signaling, by inhibiting IB phosphorylation and subsequent p65 release and translocation into the cell nucleus. Of clinical interest, the present study revealed mechanisms involved in inflammatory cytokine-inhibited osteogenesis, and it highlights the potential of cordycepin to promote the osteogenesis of human ADMSCs in cell-based therapy for inflammatory bone diseases.