PMID- 26066979
OWN - NLM
STAT- MEDLINE
DCOM- 20160606
LR  - 20181113
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 5
DP  - 2015 Jun 12
TI  - COX2 is involved in hypoxia-induced TNF-alpha expression in osteoblast.
PG  - 10020
LID - 10.1038/srep10020 [doi]
LID - 10020
AB  - Bone regeneration involves a series of events in a coordinated manner, including 
      recruitment of mesenchymal stem cells, induction of immune response, inflammatory 
      activity and vascular ingrowth. The microenvironment of bone regeneration is 
      hypoxic. Low oxygen tension (hypoxia) promotes the upregulation of several 
      signaling molecules. The primary mediating factor is the hypoxia-inducible 
      factor-1 (HIF-1). Hypoxia stimulates the expression of a variety of cytokines 
      from inflammatory cells, fibroblasts, endothelial cells, and osteoblasts. TNF-alpha 
      is a key proinflammatory cytokine. The molecular events involved in osteoblast 
      dysfunction under hypoxia are not fully understood. This study determined the 
      effects of hypoxia on TNF-alpha in osteoblasts, and molecular mechanisms were 
      explored. We observed that hypoxia induced TNF-alpha expression in a time-dependent 
      manner in osteoblasts. Experiments using a potent HIF-1alpha activator DFO 
      demonstrated that hypoxia-induced TNF-alpha was mediated by HIF-1-alpha. In addition, 
      this study showed that hypoxia activated cyclooxygenase-2 (COX2) expression along 
      with TNF-alpha. Inhibition experiments using COX2 inhibitor N398 indicated that COX2 
      was involved in hypoxia-mediated TNF-alpha expression, and this observation was 
      further confirmed by Small interfering RNA against COX2. On the other hand, TNF-alpha 
      didn't lead to the activation of COX2 expression. We conclude that COX2 is 
      involved in hypoxia-induced TNF-alpha expression in osteoblast.
FAU - Xing, Yonggang
AU  - Xing Y
AD  - Department of Spine, Beijing JiShuiTan Hospital, Beijing, 100035, China.
FAU - Wang, Renxian
AU  - Wang R
AD  - Beijing Laboratory of Biomedical Materials, Laboratory of Bone Tissue 
      Engineering, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      JiShuiTan Hospital, Beijing 100035, China.
FAU - Chen, Dafu
AU  - Chen D
AD  - Beijing Laboratory of Biomedical Materials, Laboratory of Bone Tissue 
      Engineering, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      JiShuiTan Hospital, Beijing 100035, China.
FAU - Mao, Jianping
AU  - Mao J
AD  - Department of Spine, Beijing JiShuiTan Hospital, Beijing, 100035, China.
FAU - Shi, Rui
AU  - Shi R
AD  - Beijing Laboratory of Biomedical Materials, Laboratory of Bone Tissue 
      Engineering, Beijing Research Institute of Traumatology and Orthopaedics, Beijing 
      JiShuiTan Hospital, Beijing 100035, China.
FAU - Wu, Zhihong
AU  - Wu Z
AD  - Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking 
      Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, 
      China.
FAU - Kang, Jun
AU  - Kang J
AD  - Department of Periodontology, School and Hospital of Stomatology, Peking 
      University, Beijing, 100081, China.
FAU - Tian, Wei
AU  - Tian W
AD  - Department of Spine, Beijing JiShuiTan Hospital, Beijing, 100035, China.
FAU - Zhang, Chi
AU  - Zhang C
AD  - Bone Research Laboratory, University of Texas Southwestern Medical Center, 
      Dallas, Texas 75390, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150612
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 1.14.99.- (Ptgs2 protein, mouse)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - Animals
MH  - Cell Hypoxia/drug effects
MH  - Cell Line
MH  - Cyclooxygenase 2/*metabolism
MH  - Cyclooxygenase 2 Inhibitors/pharmacology
MH  - *Gene Expression Regulation
MH  - Mice
MH  - Osteoblasts/cytology/*metabolism
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
PMC - PMC4464352
EDAT- 2015/06/13 06:00
MHDA- 2016/06/09 06:00
PMCR- 2015/06/12
CRDT- 2015/06/13 06:00
PHST- 2015/01/11 00:00 [received]
PHST- 2015/03/25 00:00 [accepted]
PHST- 2015/06/13 06:00 [entrez]
PHST- 2015/06/13 06:00 [pubmed]
PHST- 2016/06/09 06:00 [medline]
PHST- 2015/06/12 00:00 [pmc-release]
AID - srep10020 [pii]
AID - 10.1038/srep10020 [doi]
PST - epublish
SO  - Sci Rep. 2015 Jun 12;5:10020. doi: 10.1038/srep10020.