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.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117 Exp+Ther+Med
2017 ; 14
(3
): 2235-2240
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Triptolide inhibits the function of TNF-? in osteoblast differentiation by
inhibiting the NF-?B signaling pathway
#MMPMID28962148
Liu SP
; Wang GD
; Du XJ
; Wan G
; Wu JT
; Miao LB
; Liang QD
Exp Ther Med
2017[Sep]; 14
(3
): 2235-2240
PMID28962148
show ga
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)-? significantly decreased the ALP activity (P<0.05). Notably, treatment
with the chronic inflammatory cytokine TNF-? 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-? for 3 days. The
results demonstrated that TNF-? 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-? alone, or BMP2 + TNF-? 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-?-associated
inhibition of osteoblast differentiation (P<0.01). Western blotting analysis
demonstrated that triptolide markedly inhibited the phosphorylation of nuclear
factor-?B, therefore suppressing the effects of TNF-?. In summary, triptolide is
able to reverse the TNF-?-associated suppression of osteoblast differentiation,
suggesting that triptolide treatment may have a positive effect on bone
remodeling and fracture repairing.