Naringin rescued the TNF-α-induced inhibition of osteogenesis of bone marrow-derived mesenchymal stem cells by depressing the activation of NF-D0B signaling pathway

Naringin exhibits antiinflammatory activity and is shown to induce bone formation. Yet the impact of naringin on inflammation-affected bone marrow-derived mesenchymal stem cell (BM-MSC), a promising tool for the regenerative treatment of bone injury, remained to be investigated. We first cultured and characterized the BM-MSCs in vitro and observe the effects of treatments of TNF-alpha, naringin, or the combination of both on osteogenic differentiation. TNF-alpha administered at the concentration of 20 ng/ml results in significant reductions in MSC's cell survival, alkaline phosphatase activity and expressions of two osteogenic genes, Runx2 and Osx. Simultaneous treatment of both TNF-alpha and naringin is able to rescue such reductions. Further mechanistic studies indicate that TNF-alpha treatment activates the NF-(DB)-B-0 signaling pathway, evidenced by elevated p-(IDB)-B-0 alpha level as well as the increased nuclear fraction of NF-(DB)-B-0 subunit, p65. Finally, treatment with both TNF-alpha and naringin decreases expressions of p-(IDB)-B-0 alpha and nuclear p65, and thus represses NF-(DB)-B-0 pathway activated by sole TNF-alpha treatment. Our findings provide a molecular basis by which naringin restores the TNF-alpha-induced damage in MSCs and provide novel insights into the application of naringin in the MSC-based treatments for inflammation-induced bone injury.