title: COX2 is involved in hypoxia-induced TNF-α expression in osteoblast.
abstract: 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-α 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-α in osteoblasts, and molecular mechanisms were explored. We observed that hypoxia induced TNF-α expression in a time-dependent manner in osteoblasts. Experiments using a potent HIF-1α activator DFO demonstrated that hypoxia-induced TNF-α was mediated by HIF-1-α. In addition, this study showed that hypoxia activated cyclooxygenase-2 (COX2) expression along with TNF-α. Inhibition experiments using COX2 inhibitor N398 indicated that COX2 was involved in hypoxia-mediated TNF-α expression, and this observation was further confirmed by Small interfering RNA against COX2. On the other hand, TNF-α didn't lead to the activation of COX2 expression. We conclude that COX2 is involved in hypoxia-induced TNF-α expression in osteoblast.
authors.affiliation: Department of Spine, Beijing JiShuiTan Hospital, Beijing, 100035, China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Xing
authors.affiliation: Beijing Laboratory of Biomedical Materials, Laboratory of Bone Tissue Engineering, Beijing Research Institute of Traumatology and Orthopaedics, Beijing JiShuiTan Hospital, Beijing 100035, China.
authors.forename: Renxian
authors.initials: R
authors.lastname: Wang
authors.affiliation: Beijing Laboratory of Biomedical Materials, Laboratory of Bone Tissue Engineering, Beijing Research Institute of Traumatology and Orthopaedics, Beijing JiShuiTan Hospital, Beijing 100035, China.
authors.forename: Dafu
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Spine, Beijing JiShuiTan Hospital, Beijing, 100035, China.
authors.forename: Jianping
authors.initials: J
authors.lastname: Mao
authors.affiliation: Beijing Laboratory of Biomedical Materials, Laboratory of Bone Tissue Engineering, Beijing Research Institute of Traumatology and Orthopaedics, Beijing JiShuiTan Hospital, Beijing 100035, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Shi
authors.affiliation: Department of Orthopedic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Department of Periodontology, School and Hospital of Stomatology, Peking University, Beijing, 100081, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Kang
authors.affiliation: Department of Spine, Beijing JiShuiTan Hospital, Beijing, 100035, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Tian
authors.affiliation: Bone Research Laboratory, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015687:Cell Hypoxia / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D014409:Tumor Necrosis Factor-alpha; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2