1. Carbon Monoxide Inhibits Receptor Activator of NF-κB (RANKL)-Induced Osteoclastogenesis.
- Author
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Tseng FJ, Chia WT, Wang CH, Shyu JF, Gou GH, Shui HA, Sytwu HK, Pan RY, and Weng CF
- Subjects
- Acid Phosphatase genetics, Acid Phosphatase metabolism, Administration, Inhalation, Animals, Apoptosis drug effects, Arthritis, Experimental genetics, Arthritis, Experimental metabolism, Arthritis, Experimental pathology, Caspase 3 genetics, Caspase 3 metabolism, Cell Differentiation drug effects, Cell Line, Cell Proliferation drug effects, Chromans pharmacology, Gene Expression Regulation, Isoenzymes genetics, Isoenzymes metabolism, Macrophages drug effects, Macrophages metabolism, Macrophages pathology, Male, Mice, Mice, Inbred BALB C, Osteoclasts metabolism, Osteoclasts pathology, PPAR gamma antagonists & inhibitors, PPAR gamma genetics, PPAR gamma metabolism, RANK Ligand pharmacology, Signal Transduction, Synovial Membrane drug effects, Synovial Membrane metabolism, Synovial Membrane pathology, Tartrate-Resistant Acid Phosphatase, Thiazolidinediones pharmacology, Troglitazone, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Antimetabolites pharmacology, Arthritis, Experimental drug therapy, Carbon Monoxide pharmacology, Osteoclasts drug effects, RANK Ligand antagonists & inhibitors
- 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., (© 2015 S. Karger AG, Basel.)
- Published
- 2015
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