Abstract
Nuclear factor kappa B (NF-κB) regulates inflammatory gene expression and represents a likely target for novel disease treatment approaches, including skeletal disorders. Several plant-derived sesquiterpene lactones can inhibit the activation of NF-κB. Parthenolide (PTL) is an abundant sesquiterpene lactone, found in Mexican Indian Asteraceae family plants, with reported anti-inflammatory activity, through the inhibition of a common step in the NF-κB activation pathway. This study examined the effects of PTL on the enhanced, in vitro, osteogenic phenotypes of human periosteum-derived cells (hPDCs), mediated by the inflammatory cytokine tumor necrosis factor (TNF)-α. PTL had no significant effects on hPDC viability or osteoblastic activities, whereas TNF-α had positive effects on the in vitro osteoblastic differentiation of hPDCs. c-Jun N-terminal kinase (JNK) signaling played an important role in the enhanced osteoblastic differentiation of TNF-α-treated hPDCs. Treatment with 1 µM PTL did not affect TNF-α-treated hPDCs; however, 5 and 10 µM PTL treatment decreased the histochemical detection and activity of alkaline phosphatase (ALP), alizarin red-positive mineralization, and the expression of ALP and osteocalcin mRNA. JNK phosphorylation decreased significantly in TNF-α-treated hPDCs pretreated with PTL. These results suggested that PTL exerts negative effects on the increased osteoblastic differentiation of TNF-α-treated hPDCs by inhibiting JNK signaling.
Highlights
Stromal stem cells possess the characteristic of “stemness”, defined as the capacity for self-renewal and the ability to generate differentiated progeny and produce diverse cell types
Combined with the effects of mitogen-activated protein kinases (MAPKs) inhibitors on the in vitro osteoblastic differentiation of the human periosteum-derived cells (hPDCs) treated with Tumor necrosis factor (TNF)-α, our results suggested that the negative effects of PTL were primarily associated with the inhibition of cells pretreated with PTL
Combined with the effects of MAPK inhibitors on the in vitro osteoblastic differentiation of the hPDCs treated with TNF-α, our results suggested that the nIengt.aJ.tMivoel
Summary
Stromal stem cells possess the characteristic of “stemness”, defined as the capacity for self-renewal and the ability to generate differentiated progeny and produce diverse cell types. The supplementation and additional management of mesenchymal stem cells (MSCs), including the pretreatment of MSCs with growth factors, such as bone morphogenetic proteins (BMPs) or pro-regenerative cytokines, such as transforming growth factor β (TGF-β), have been demonstrated to enhance the abilities of MSCs to differentiate into osteoblasts, which is necessary to improve the likelihood of using MSCs for tissue repair [5,6,7,8]. The influence of TNF-α on the osteoblastic differentiation of osteoprecursor cells has been reported to actively direct MSCs away from an osteoblastic fate [9,10,11]. The stimulatory effects of this cytokine, including the recruitment of MSCs and osteoblasts, have been reported [12,13,14]
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