Mollugin from Rubea cordifolia suppresses receptor activator of nuclear factor-κB ligand-induced osteoclastogenesis and bone resorbing activity in vitro and prevents lipopolysaccharide-induced bone loss in vivo.

Abstract

Osteopenic diseases, such as osteoporosis, are characterized by progressive and excessive bone resorption mediated by enhanced receptor activator of nuclear factor-κB ligand (RANKL) signaling. Therefore, downregulation of RANKL downstream signals may be a valuable approach for the treatment of bone loss-associated disorders. In this study, we investigated the effects of the naphthohydroquinone mollugin on osteoclastogenesis and its function in vitro and in vivo. Mollugin efficiently suppressed RANKL-induced osteoclast differentiation of bone marrow macrophages (BMMs) and bone resorbing activity of mature osteoclasts by inhibiting RANKL-induced c-Fos and NFATc1 expression. Mollugin reduced the phosphorylation of signaling pathways activated in the early stages of osteoclast differentiation, including the MAP kinase, Akt, and GSK3β and inhibited the expression of different genes associated with osteoclastogenesis, such as OSCAR, TRAP, DC-STAMP, OC-STAMP, integrin αν, integrin β3, cathepsin K, and ICAM-1. Furthermore, mice treated with mollugin showed significant restoration of lipopolysaccharide (LPS)-induced bone loss as indicated by micro-CT and histological analysis of femurs. Consequently, these results suggested that mollugin could be a novel therapeutic candidate for bone loss-associated disorders including osteoporosis, rheumatoid arthritis, and periodontitis.

• Authors: Jong Min Baek, Ju-Young Kim, Youngeun Jung, Seong-Hee Moon, Min Kyu Choi, Seong Hwan Kim, Myeung Su Lee, Ikyon Kim, Jaemin Oh
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 22 Issue 1 Pg. 27-35 (Jan 15 2015) ISSN: 1618-095X [Electronic] Germany
• PMID: 25636867 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier GmbH. All rights reserved.

Chemical References

• Lipopolysaccharides
• Pyrans
• RANK Ligand
• Tnfsf11 protein, mouse
• rubimaillin

Topics

• Animals
• Bone Resorption (drug therapy)
• Cell Differentiation (drug effects)
• Cells, Cultured
• Lipopolysaccharides
• Macrophages (drug effects)
• Mice, Inbred ICR
• Osteoclasts (drug effects)
• Pyrans (pharmacology)
• RANK Ligand (metabolism)
• Rubia (chemistry)
• Signal Transduction (drug effects)