Research article summary (published 30 Oct 2009):

Diclofenac sodium inhibits NFkappaB transcription in osteoclasts.

Full 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.

Author information

Author/s: Karakawa, A (A); Fukawa, Y (Y); Okazaki, M (M); Takahashi, K (K); Sano, T (T); Amano, H (H); Yamamoto, M (M); Yamada, S (S);

Affiliation: Department of Pharmacology, Showa University School of Dentistry, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. a-karakawa(-atsign-)dent.showa-u.ac.jp

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Journal of dental research (J Dent Res), published in United States. (Language: eng)

Reference: 2009-Nov; vol 88 (issue 11) : pp 1042-7

Dates: Created 2009/10/15; Completed 2009/10/29;

PMID: 19828894, status: MEDLINE (last retrieval date: 10/29/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

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

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

Associated Chemicals: Anti-Inflammatory Agents, Non-Steroidal (0) ; Biological Markers (0) ; Integrin alphaV (0) ; Integrin beta3 (0) ; Isoenzymes (0) ; NF-kappa B p50 Subunit (0) ; Rela protein, mouse (0) ; Transcription Factor RelA (0) ; Nfkb1 protein, mouse (147257-52-1) ; Diclofenac (15307-86-5) ; tartrate-resistant acid phosphatase (EC 3.1.3.-) ; Acid Phosphatase (EC 3.1.3.2) ; Cathepsins (EC 3.4.-) ; Cysteine Endopeptidases (EC 3.4.22.-) ; cathepsin K (EC 3.4.22.-)

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