Bergapten suppresses RANKL-induced osteoclastogenesis and ovariectomy-induced osteoporosis via suppression of NF-κB and JNK signaling pathways.

Abstract

Bergapten (BP), derived from Cnidium monnieri (L.) Cusson, is an ingredient widely used in traditional Chinese medicine and has important biological and pharmacological activities. However, the effect of BP on ovariectomy-induced osteoporosis and the underlying mechanism are not entirely clear. In this study, we investigated the effects of BP on ovariectomy-induced osteoporosis and receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis in vivo and in vitro, and explored the underlying mechanism. We found that BP treatment exerted beneficial effects on ovariectomy-induced osteoporosis in vivo. Further, BP attenuated osteoclastogenesis in bone marrow macrophages (BMMs) and RAW264.7 cells without any cytotoxicity. Additionally, BP specifically inhibited RANKL-induced NF-κB and JNK signaling,but did not suppress p38 and ERK. At the mRNA level, BP inhibits the OC-associated transcription factor NFATc1 and c-fos, thereby affecting the expression of OC differentiation-related genes. Moreover, BP disrupted the formation of F-actin rings, which are important for bone-resorbing activity, and impairs OC bone resorption. Therefore, BP may be a useful alternative therapy for post-menopausal osteoporosis.

• Authors: Guiping Chen, Qiang Xu, Min Dai, Xuqiang Liu
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 509 Issue 2 Pg. 329-334 (02 05 2019) ISSN: 1090-2104 [Electronic] United States
• PMID: 30579598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• Actins
• Bone Density Conservation Agents
• NF-kappa B
• NFATC Transcription Factors
• Nfatc1 protein, mouse
• Proto-Oncogene Proteins c-fos
• RANK Ligand
• Tnfsf11 protein, mouse
• 5-Methoxypsoralen
• Mapk1 protein, mouse
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases

Topics

• 5-Methoxypsoralen (pharmacology)
• Actins (genetics, metabolism)
• Animals
• Bone Density Conservation Agents (pharmacology)
• Bone Resorption (etiology, genetics, metabolism, prevention & control)
• Female
• Gene Expression Regulation
• Humans
• MAP Kinase Signaling System (drug effects)
• Macrophages (drug effects, metabolism, pathology)
• Mice
• Mice, Inbred C57BL
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• NF-kappa B (antagonists & inhibitors, genetics, metabolism)
• NFATC Transcription Factors (genetics, metabolism)
• Osteoclasts (drug effects, metabolism, pathology)
• Osteogenesis (drug effects, genetics)
• Osteoporosis (etiology, genetics, metabolism, prevention & control)
• Ovariectomy (adverse effects)
• Primary Cell Culture
• Proto-Oncogene Proteins c-fos (genetics, metabolism)
• RANK Ligand (antagonists & inhibitors, genetics, metabolism, pharmacology)
• RAW 264.7 Cells
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)