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Carbon Monoxide Inhibits Receptor Activator of NF-κB (RANKL)-Induced Osteoclastogenesis.
- Source :
-
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2015; Vol. 36 (3), pp. 1250-8. Date of Electronic Publication: 2015 Jul 01. - Publication Year :
- 2015
-
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.<br />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.<br />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.<br />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.<br /> (© 2015 S. Karger AG, Basel.)
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 1421-9778
- Volume :
- 36
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 26138885
- Full Text :
- https://doi.org/10.1159/000430294