PMID- 26088424
OWN - NLM
STAT- MEDLINE
DCOM- 20151105
LR  - 20150821
IS  - 1544-0591 (Electronic)
IS  - 0022-0345 (Linking)
VI  - 94
IP  - 9
DP  - 2015 Sep
TI  - Effects of TNF-alpha on Cementoblast Differentiation, Mineralization, and Apoptosis.
PG  - 1225-32
LID - 10.1177/0022034515590349 [doi]
AB  - Tumor necrosis factor-alpha (TNF-alpha) is involved in various inflammatory processes, 
      including periodontitis. Although the influences of TNF-alpha on periodontal ligament 
      fibroblasts and osteoblasts have been widely documented, its effects on 
      cementoblasts, the cells responsible for cementum production, remain largely 
      unknown. In this study, we found that TNF-alpha suppressed the mineralization ability 
      of cementoblasts by inhibiting differentiation and inducing apoptosis. Various 
      signaling pathways, such as p53, PP2AC, p38, Erk1/2, JNK, PI3K-Akt, and NF-kappaB, 
      were activated during this process. The use of a specific inhibitor and siRNA 
      transfection confirmed that the effects of TNF-alpha on differentiation and apoptosis 
      in cementoblasts were partially abrogated by inhibiting p53 activity. By 
      contrast, the effects of TNF-alpha were even exacerbated by the inhibition of the 
      p38, Erk1/2, JNK, PI3K-Akt, and NF-kappaB pathways. Moreover, p53 activity was 
      further enhanced by blocking the p38, Erk1/2, JNK, and PI3K-Akt signaling 
      pathways. Taken together, these results suggested that the differentiation 
      inhibition and apoptosis in cementoblasts induced by TNF-alpha were partially 
      dependent on p53 activity. The p38, Erk1/2, JNK, PI3K-Akt, and NF-kappaB pathways 
      were also activated but acted as balancing players to limit rather than conduct 
      the negative effects of TNF-alpha. These balancing effects were dependent, or at 
      least partially dependent, on p53, except for the NF-kappaB pathway.
CI  - (c) International & American Associations for Dental Research 2015.
FAU - Wang, Y L
AU  - Wang YL
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - He, H
AU  - He H
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China drhehong@hotmail.com 
      liuzhijian@hotmail.com.
FAU - Liu, Z J
AU  - Liu ZJ
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Cao, Z G
AU  - Cao ZG
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Wang, X Y
AU  - Wang XY
AD  - State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese 
      Academy of Sciences, Beijing, China.
FAU - Yang, K
AU  - Yang K
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Fang, Y
AU  - Fang Y
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Han, M
AU  - Han M
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Zhang, C
AU  - Zhang C
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
FAU - Huo, F Y
AU  - Huo FY
AD  - The State Key Laboratory Breeding Base of Basic Science of Stomatology 
      (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education, School & 
      Hospital of Stomatology, Wuhan University, Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150618
PL  - United States
TA  - J Dent Res
JT  - Journal of dental research
JID - 0354343
RN  - 0 (NF-kappa B)
RN  - 0 (TP53 protein, human)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.1.3.1 (Alkaline Phosphatase)
SB  - IM
MH  - Alkaline Phosphatase/metabolism
MH  - Apoptosis/*physiology
MH  - Calcification, Physiologic/*physiology
MH  - Cell Differentiation/*physiology
MH  - Cell Line, Transformed
MH  - Dental Cementum/*cytology/enzymology/metabolism
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/antagonists & inhibitors/metabolism
MH  - NF-kappa B/antagonists & inhibitors/metabolism
MH  - Tumor Necrosis Factor-alpha/*physiology
MH  - Tumor Suppressor Protein p53/antagonists & inhibitors/metabolism
OTO - NOTNLM
OT  - dental cementum
OT  - guided tissue regeneration
OT  - osterix protein
OT  - periodontitis
OT  - signal transduction
OT  - tumor suppressor protein p53
EDAT- 2015/06/20 06:00
MHDA- 2015/11/06 06:00
CRDT- 2015/06/20 06:00
PHST- 2015/06/20 06:00 [entrez]
PHST- 2015/06/20 06:00 [pubmed]
PHST- 2015/11/06 06:00 [medline]
AID - 0022034515590349 [pii]
AID - 10.1177/0022034515590349 [doi]
PST - ppublish
SO  - J Dent Res. 2015 Sep;94(9):1225-32. doi: 10.1177/0022034515590349. Epub 2015 Jun 
      18.