PMID- 24360989 OWN - NLM STAT- MEDLINE DCOM- 20140331 LR - 20140203 IS - 1090-2422 (Electronic) IS - 0014-4827 (Linking) VI - 321 IP - 2 DP - 2014 Feb 15 TI - Tumor necrosis factor stimulates osteoclastogenesis from human bone marrow cells under hypoxic conditions. PG - 167-77 LID - S0014-4827(13)00513-2 [pii] LID - 10.1016/j.yexcr.2013.11.020 [doi] AB - Bone homeostasis is maintained by the balance between osteoblastic bone formation and osteoclastic bone resorption. In this study, we used human bone marrow cells (BMCs) to investigate the role of hypoxic exposure on human osteoclast (OC) formation in the presence of tumor necrosis factor (TNF). Exposing the BMCs to 3%, 5%, or 10% O2 in the presence of receptor activator of NF-kappaB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) generated tartrate-resistant acid phosphatase (TRAP)-positive multinuclear cells, consistent with OCs. The addition of TNF under hypoxic conditions generated significantly greater numbers of mature OCs with more nuclei than OCs generated under normoxic conditions. Longer initial hypoxic exposure increased the number of OC precursor cells and facilitated the differentiation of OC precursor cells into multinucleated OCs. Quantitative RT-PCR analysis revealed that RANKL and TNFR1 were expressed at higher levels in non-OC cells from BMCs under hypoxic conditions than under normoxic conditions. Furthermore, to confirm the involvement of TNF-induced signaling, we examined the effects of blocking antibodies against TNFR1 and TNFR2 on OC formation under hypoxic conditions. The TNFR1 antibody was observed to significantly suppress OC formation. These results suggest that hypoxic exposure plays an important role in TNF-induced osteoclastogenesis from human BMCs. CI - Copyright (c) 2013 Elsevier Inc. All rights reserved. FAU - Nomura, Takayuki AU - Nomura T AD - Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya 464-8651, Japan; Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. FAU - Aoyama, Mineyoshi AU - Aoyama M AD - Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. Electronic address: ao.mine@med.nagoya-cu.ac.jp. FAU - Waguri-Nagaya, Yuko AU - Waguri-Nagaya Y AD - Department of Orthopaedic Surgery, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. FAU - Goto, Yoh AU - Goto Y AD - Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya 464-8651, Japan; Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. FAU - Suzuki, Mieko AU - Suzuki M AD - Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. FAU - Miyazawa, Ken AU - Miyazawa K AD - Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya 464-8651, Japan. FAU - Asai, Kiyofumi AU - Asai K AD - Department of Molecular Neurobiology, Nagoya City University Graduate School of Medical Sciences, Mizuho-ku, Nagoya 467-8601, Japan. FAU - Goto, Shigemi AU - Goto S AD - Department of Orthodontics, School of Dentistry, Aichi-Gakuin University, Chikusa-ku, Nagoya 464-8651, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20131217 PL - United States TA - Exp Cell Res JT - Experimental cell research JID - 0373226 RN - 0 (Tumor Necrosis Factor-alpha) RN - S88TT14065 (Oxygen) SB - IM MH - Bone Marrow Cells/*drug effects/physiology MH - Cell Differentiation/*drug effects MH - Cell Hypoxia/physiology MH - Cells, Cultured MH - Dose-Response Relationship, Drug MH - Gene Expression Regulation/drug effects MH - Humans MH - Osteoclasts/*drug effects/physiology MH - Oxygen/pharmacology MH - Oxygen Consumption/physiology MH - Time Factors MH - Tumor Necrosis Factor-alpha/*pharmacology OTO - NOTNLM OT - Human bone marrow cells (BMCs) OT - Human osteoclast OT - Hypoxia OT - Tumor necrosis factor (TNF) EDAT- 2013/12/24 06:00 MHDA- 2014/04/01 06:00 CRDT- 2013/12/24 06:00 PHST- 2013/07/18 00:00 [received] PHST- 2013/11/06 00:00 [revised] PHST- 2013/11/27 00:00 [accepted] PHST- 2013/12/24 06:00 [entrez] PHST- 2013/12/24 06:00 [pubmed] PHST- 2014/04/01 06:00 [medline] AID - S0014-4827(13)00513-2 [pii] AID - 10.1016/j.yexcr.2013.11.020 [doi] PST - ppublish SO - Exp Cell Res. 2014 Feb 15;321(2):167-77. doi: 10.1016/j.yexcr.2013.11.020. Epub 2013 Dec 17.