Send to

Choose Destination
Int Endod J. 2015 Jul;48(7):705-16. doi: 10.1111/iej.12396. Epub 2014 Nov 5.

TNF-α and LPS activate angiogenesis via VEGF and SIRT1 signalling in human dental pulp cells.

Author information

Department of Prosthodontics, Dongatn Sacred Heart Hospital, Hallym University, Dongtan, Korea.
Department of Oral Medicine, School of Dentistry, Kyung Hee University, Seoul, Korea.
Department of Oral and Maxillofacial Pathology, Research Center for Tooth and Periodontal Regeneration (MRC), School of Dentistry, Kyung Hee University, Seoul, Korea.
Department of Conservative Dentistry, School of Dentistry, Kyung Hee University, Seoul, Korea.



To assess whether SIRT1 and VEGF are responsible for tumour necrosis factor-α (TNF-α) and lipopolysaccharide (LPS)-induced angiogenesis and to examine the molecular mechanism(s) of action in human dental pulp cells (HDPCs).


Immortalized HDPCs obtained from Prof. Takashi Takata (Hiroshima University, Japan) were treated with LPS (1 μg mL(-1) ) and TNF-α (10 ng mL(-1) ) for 24 h. mRNA and protein levels were examined by RT-PCR and Western blotting, respectively. Migration and tube formation were examined in human umbilical vein endothelial cells (HUVECs). The data were analysed by one-way anova. Statistical analysis was performed at α = 0.05.


LPS and TNF-α upregulated VEGF and SIRT1 mRNA and protein levels. Inhibition of SIRT1 activity by sirtinol and SIRT1 siRNA or inhibition of the VEGF receptor by CBO-P11 significantly attenuated LPS + TNF-α-stimulated MMPs production in HDPCs, as well as migration and tube formation in HUVECs (P < 0.05). Furthermore, sirtinol, SIRT1 siRNA and CBO-P11 attenuated phosphorylation of Akt, extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK) and the nuclear translocation of NF-κB p65. Pre-treatment with inhibitors of p38, ERK, JNK, PI3K and NF-κB decreased LPS + TNF-α-induced VEGF and SIRT1 expression, MMPs activity in HDPCs and angiogenesis (P < 0.05) in HUVECs.


TNF-α and LPS led to upregulation of VEGF and SIRT1, and subsequent upregulation of MMP-2 and MMP-9 production, and promote angiogenesis via pathways involving PI3K, p38, ERK, JNK and NF-κB. The results suggest that inhibition of SIRT1 and VEGF might attenuate pro-inflammatory mediator-induced pulpal disease.


angiogenesis; human dental pulp cells; lipopolysaccharide; silent information regulator protein 1; tumour necrosis factor-α; vascular endothelial growth factor

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center