Curcumol suppresses RANKL-induced osteoclast formation by attenuating the JNK signaling pathway.

Abstract

Osteoclasts, derived from hemopoietic progenitors of the monocyte/macrophage lineage, have a unique role in bone resorption, and are considered a potential therapeutic target in the treatment of such pathologic bone diseases as osteoporosis, rheumatoid arthritis, and periodontitis. In the present study, we demonstrate that curcumol, one of the major components of the essential oil of Rhizoma Curcumae, exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner. In addition, RANKL-induced mRNA expression of osteoclast-specific genes, such as tartrate-resistant acid phosphatase, calcitonin receptor, and cathepsin K, is prominently reduced in the presence of curcumol. Furthermore, the molecular mechanism of action was investigated, and curcumol inhibited osteoclastogenesis by specifically impairing RANKL-induced c-Jun N-terminal kinase (JNK)/activator protein-1 (AP-1) signaling, which was further identified in rescue studies by means of anisomycin, a JNK signaling-specific activator. Taken together, these findings suggest that curcumol suppresses RANKL-induced osteoclast differentiation through the JNK/AP-1 signaling pathway, and may be useful as a therapeutic treatment for bone resorption-associated diseases.

• Authors: Mingxiang Yu, Xianying Chen, Chaoyang Lv, Xilu Yi, Yao Zhang, Mengjuan Xue, Shunmei He, Guoying Zhu, Hongfu Wang
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 447 Issue 2 Pg. 364-70 (May 02 2014) ISSN: 1090-2104 [Electronic] United States
• PMID: 24732351 (Publication Type: Journal Article)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Drugs, Chinese Herbal
• NFATC Transcription Factors
• Nfatc1 protein, mouse
• RANK Ligand
• Sesquiterpenes
• Transcription Factor AP-1
• Anisomycin
• curcumol

Topics

• Animals
• Anisomycin (pharmacology)
• Cell Differentiation (drug effects)
• Cell Survival (drug effects)
• Drugs, Chinese Herbal (pharmacology)
• Gene Expression (drug effects)
• MAP Kinase Signaling System (drug effects)
• Mice
• NFATC Transcription Factors (metabolism)
• Osteoclasts (cytology, drug effects, physiology)
• RANK Ligand (pharmacology)
• Sesquiterpenes (pharmacology)
• Transcription Factor AP-1 (metabolism)