Triptolide inhibits the function of TNF-α in osteoblast differentiation by inhibiting the NF-κB signaling pathway

Abstract

Abstract. Chronic inflammation often delays fracture healing or leads to bone nonunion. Effectively suppressing pathological inflammation is crucial for fracture healing or bone remodeling. Triptolide, which is a diterpenoid epoxide, is the major active component of the Thunder God Vine, Tripterygium wilfordii. The aim of the present study was to investigate the role of triptolide in osteoblast differentiation and explore the molecular mechanisms of triptolide in fracture healing. Alkaline phosphatase (ALP) activity was used to evaluate osteoblast differentiation. ALP activity was measured via histochemical staining and western blotting was used to determine the expression of factors associated with inflammation. C2C12 cells were initially treated with 200 ng/ml bone morphogenetic protein (BMP)-2 alone for 3 days, which caused a significant increase in ALP activity (P<0.01). However, treatment with tumor necrosis factor (TNF)-α significantly decreased the ALP activity (P<0.05). Notably, treatment with the chronic inflammatory cytokine TNF-α significantly decreased the effect of BMP-2 in C2C12 cells compared with BMP-2 treatment alone (P<0.01). C2C12 cells were treated with increasing concentrations of BMP-2 or TNF-α for 3 days. The results demonstrated that TNF-α treatment significantly inhibited BMP-2-induced osteoblast differentiation in a dose-dependent manner (P<0.01). The role of triptolide in BMP-2-induced osteoblast differentiation was also examined. Cells were treated with BMP-2, BMP-2 + TNF-α alone, or BMP2 + TNF-α with increasing concentrations of triptolide (4, 8 or 16 ng/ml). After 3 days, the results of ALP activity revealed that triptolide significantly reversed the TNF-α-associated inhibition of osteoblast differentiation (P<0.01). Western blotting analysis demonstrated that triptolide markedly inhibited the phosphorylation of nuclear factor-κB, therefore suppressing the effects of TNF-α. In summary, triptolide is able to reverse the TNF-α-associated suppression of osteoblast differentiation, suggesting that triptolide treatment may have a positive effect on bone remodeling and fracture repairing.

<p>Effects Of Triptolide On Tooth Movement And Root Resorption In Rats</p>

“…An in vitro study demonstrated the suppressive effect of triptolide on osteoblast proliferation and mineralization 35. Nevertheless, in another in vitro study, triptolide was found to be able to reverse TNF-α-associated suppression of osteoblast differentiation 36. The process of bone formation plays an important role in OTM, which could sustain the structural integrity of alveolar bone.…”

Ras associated with diabetes may play a role in fracture nonunion development in rats

“…These results suggested that the regulation of Rad gene expression levels in nonunions is associated with TNF-α but not with PDGF. Chronic inflammation, which involves potent pro-inflammatory cytokines such as TNF-α, is well known as a factor that can lead to the development of nonunion [30]. High concentrations of TNF-α have been reported to inhibit osteoblast differentiation [31], and one of the mechanisms is thought to be the downregulation of preosteoblast epidermal growth factor-like repeat protein by meprin, A5 protein, and receptor protein-tyrosine phosphatase l domain (POEM) [32].…”

The Effect of Triptolide in Rheumatoid Arthritis: From Basic Research towards Clinical Translation

“…Research by Xu et al indicated that TP could enhance the expression of IL-10 and TGF-β1 secreted by Tregs in vitro, which further inhibit osteoclast formation and bone resorption [ 6 ]. In another study, TP was found be able to reverse TNF-α-associated suppression of osteoblast differentiation, suggesting that TP might have a positive effect on bone remodeling [ 56 ].…”