Resveratrol rescued the TNF-α-induced impairments of osteogenesis of bone-marrow derived mesenchymal stem cells and inhibited the TNF-α-activated NF-кB signaling pathway

Resveratrol rescued the TNF-α-induced impairments of osteogenesis of bone-marrow derived mesenchymal stem cells and inhibited the TNF-α-activated NF-кB signaling pathway

Abstract

Resveratrol, trans-3,4 '-trihydroxystilbene, is a natural phytoalexin. Its anti-inflammatory activity has attracted more and more attention in clinic over the years for the treatment of inflammatory diseases. However, its effect on bone repair and new bone formation in an inflammatory microenvironment is quite little understood, especially when bone-marrow derived mesenchymal stem cells (MSCs) are used in stem cell therapy for the treatment of inflammatory bone diseases. In the present study, we investigated the effect of resveratrol on osteogenic differentiation of primary mouse bone marrow derived MSCs and potential mechanism involved when cells were exposed to TNF-α treatment. We found that resveratrol reversed the apoptotic effect of TNF-α and abrogated its inhibitory effect on osteogenic differentiation of bone marrow derived MSCs. Mechanistic studies demonstrated that resveratrol rescued the TNF-α-induced impairments of osteogenesis, and inhibited TNF-α-activated NF-κB signaling. Our study may help understand the mechanism involved in the inhibitory effect of inflammatory cytokines on osteogenic differentiation, and highlights the role of resveratrol as a potential therapeutic agent for bone repair and especially in MSC-based cell therapy for the treatment of inflammation-associated bone diseases.

Abstract

Resveratrol, trans-3,4 '-trihydroxystilbene, is a natural phytoalexin. Its anti-inflammatory activity has attracted more and more attention in clinic over the years for the treatment of inflammatory diseases. However, its effect on bone repair and new bone formation in an inflammatory microenvironment is quite little understood, especially when bone-marrow derived mesenchymal stem cells (MSCs) are used in stem cell therapy for the treatment of inflammatory bone diseases. In the present study, we investigated the effect of resveratrol on osteogenic differentiation of primary mouse bone marrow derived MSCs and potential mechanism involved when cells were exposed to TNF-α treatment. We found that resveratrol reversed the apoptotic effect of TNF-α and abrogated its inhibitory effect on osteogenic differentiation of bone marrow derived MSCs. Mechanistic studies demonstrated that resveratrol rescued the TNF-α-induced impairments of osteogenesis, and inhibited TNF-α-activated NF-κB signaling. Our study may help understand the mechanism involved in the inhibitory effect of inflammatory cytokines on osteogenic differentiation, and highlights the role of resveratrol as a potential therapeutic agent for bone repair and especially in MSC-based cell therapy for the treatment of inflammation-associated bone diseases.

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