| Abstract | A non-steroidal anti-inflammatory drug, diclofenac, acts efficiently against inflammation; however, down-regulation of diclofenac on bone remodeling has raised concerns. The inhibitory mechanisms of diclofenac are poorly understood. We hypothesized that diclofenac down-regulates osteoclast differentiation and activation via inhibition of the translocation of phosphorylated nuclear factor kappa B (NFkappaB). When osteoclasts prepared from mouse hematopoietic stem cells were treated with diclofenac, tartrateresistant acid phosphatase-positive multinucleated cells decreased in a concentration-dependent manner. Pit formation assay revealed the abolition of osteoclastic bone resorption; levels of cathepsin K transcripts, an osteoclastic resorption marker, were down-regulated time-dependently. Diclofenac induced the accumulation of the inhibitor of kappa B in cytosol, which led to suppression of the nuclear translocation of NFkappaB and phosphorylated NFkappaB. These results suggest that the novel mechanism of diclofenac for bone remodeling is associated with phosphorylated NFkappaB reduction, which regulates osteoclast differentiation and activation. |
| Authors | A Karakawa, Y Fukawa, M Okazaki, K Takahashi, T Sano, H Amano, M Yamamoto, S Yamada
(Affiliation: Department of Pharmacology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. a-karakawa at dent.showa-u.ac.jp)
|
| Journal | Journal of dental research
(J Dent Res)
Vol. 88
Issue 11
Pg. 1042-7
(Nov 2009)
ISSN: 1544-0591 [Electronic] United States |
| PMID | 19828894
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Biological Markers
- Integrin alphaV
- Integrin beta3
- Isoenzymes
- NF-kappa B p50 Subunit
- Rela protein, mouse
- Transcription Factor RelA
- Nfkb1 protein, mouse
- Diclofenac
- tartrate-resistant acid phosphatase
- Acid Phosphatase
- Cathepsins
- Cysteine Endopeptidases
- cathepsin K
|
| Topics |
- Acid Phosphatase
(analysis)
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(administration & dosage, pharmacology)
- Biological Markers
(analysis)
- Bone Resorption
(physiopathology)
- Cathepsins
(analysis)
- Cell Count
- Cell Differentiation
(drug effects)
- Cell Nucleus
(drug effects)
- Cell Survival
(drug effects)
- Cells, Cultured
- Cysteine Endopeptidases
(analysis)
- Cytosol
(drug effects)
- Diclofenac
(administration & dosage, pharmacology)
- Dose-Response Relationship, Drug
- Down-Regulation
- Hematopoietic Stem Cells
(cytology)
- Integrin alphaV
(drug effects)
- Integrin beta3
(drug effects)
- Isoenzymes
(analysis)
- Male
- Mice
- NF-kappa B p50 Subunit
(antagonists & inhibitors)
- Osteoclasts
(drug effects)
- Time Factors
- Transcription Factor RelA
(antagonists & inhibitors)
- Transcription, Genetic
(drug effects)
|
