title: Carbon Monoxide Inhibits Receptor Activator of NF-κB (RANKL)-Induced Osteoclastogenesis.
abstract: BACKGROUND
  Low concentrations of carbon monoxide (CO) have anti-inflammatory effects and can reduce bone erosion in a murine collagen-induced arthritis model. The objective of this study was to assess the effects of CO on receptor activator of NF-κB ligand (RANKL), one of the key stimulators of osteoclastogenesis.
  
  
  METHODS
  The in vivo effects of CO on RANKL expression were assessed in a collagen antibody-induced arthritis model in mice. Cell proliferation and apoptosis were assessed in the RAW246.7 cell line stimulated with RANKL and exposed to either air or CO. The number of tartrate resistant acid phosphatase (TRAP)-positive RAW246.7 cells was also examined after treatment with RANKL and the peroxisome proliferator-activated receptor gamma (PPARγ) agonist, Troglitazone.
  
  
  RESULTS
  CO reduced RANKL expression in the synovium of arthritic mice. Although CO slightly increased RAW246.7 cell proliferation, no differences in activated caspase 3 levels were detected. In addition, Troglitazone ameliorated the inhibitory effects of CO on RANKL-induced TRAP expression by RAW246.7 cells.
  
  
  CONCLUSIONS
  CO suppresses osteoclast differentiation by inhibiting the RANKL-induced activation of PPAR-γ. Given the role of the PPAR-γ/cFos (AP-1) pathway in regulating the transcription factor, NFATc1, the master regulator of osteoclastogenesis, further studies are warranted to explore CO in treating inflammatory bone disorders.
authors.affiliation: Department of Life Science and the institute of Biotechnology, National Dong Hwa University, Hualien, Taiwan, R.O.C.
authors.forename: Feng-Jen
authors.initials: FJ
authors.lastname: Tseng
authors.forename: Wei-Tso
authors.initials: WT
authors.lastname: Chia
authors.forename: Chih-Hung
authors.initials: CH
authors.lastname: Wang
authors.forename: Jia-Fwu
authors.initials: JF
authors.lastname: Shyu
authors.forename: Guo-Hau
authors.initials: GH
authors.lastname: Gou
authors.forename: Hao-Ai
authors.initials: HA
authors.lastname: Shui
authors.forename: Huey-Kang
authors.initials: HK
authors.lastname: Sytwu
authors.forename: Ru-Yu
authors.initials: RY
authors.lastname: Pan
authors.forename: Ching-Feng
authors.initials: CF
authors.lastname: Weng
mesh_terms: D000135:Acid Phosphatase / Q000235:genetics / Q000378:metabolism; D000280:Administration, Inhalation; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000963:Antimetabolites / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002248:Carbon Monoxide / Q000494:pharmacology*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002839:Chromans / Q000494:pharmacology; D005786:Gene Expression Regulation; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010010:Osteoclasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D047495:PPAR gamma / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D015398:Signal Transduction; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071681:Tartrate-Resistant Acid Phosphatase; D045162:Thiazolidinediones / Q000494:pharmacology; D000077288:Troglitazone
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000963:Antimetabolites; D002839:Chromans; D007527:Isoenzymes; D047495:PPAR gamma; D053245:RANK Ligand; D045162:Thiazolidinediones; C505689:Tnfsf11 protein, mouse; D002248:Carbon Monoxide; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase; D053148:Caspase 3; D000077288:Troglitazone