Myricetin prevents titanium particle-induced osteolysis in vivo and inhibits RANKL-induced osteoclastogenesis in vitro.

Abstract

Titanium (Ti) particle-induced periprosthetic osteolysis and subsequent aseptic loosening are a primary reason for total hip arthroplasty failure. The aim of this study was to assess the effect of myricetin on Ti particle-induced osteolysis and osteoclastogenesis. We demonstrated that myricetin, a natural plant extract, exerts potent inhibitory effects on Ti particle-induced osteolysis in a mouse calvarial model. Further histological analysis indicated that the inhibition of osteoclast formation and function, and the secretion of inflammatory factors, are key targets for therapeutic agents in the treatment of wear particle-induced osteolysis. In vitro, we found that myricetin suppressed receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation, bone resorption, and F-actin ring formation in a dose-dependent manner. Moreover, myricetin significantly reduced the expression of osteoclast-specific markers in mouse bone marrow-derived macrophages, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, the calcitonin receptor, V-ATPase d2, c-fos, and nuclear factor of activated T cells (NFAT) c1. Further investigation revealed that myricetin inhibited osteoclastogenesis through the suppression of the nuclear factor-κB (NF-κB) signaling pathway and mitogen-activated protein kinase (MAPK) pathways involving extracellular signal-regulated kinase 1/2 (ERK1/2), p38, and c-Jun N-terminal kinase 1/2 (JNK1/2). While, the inhibition of TNF-α and IL-1β secretion was another reason for the suppressive effect of myricetin on Ti particle-induced osteolysis. Collectively, these findings suggest that myricetin is a potential natural agent for the treatment of periprosthetic osteolysis and other osteoclast-related osteolytic diseases.

• Authors: Chuanlong Wu, Wengang Wang, Bo Tian, Xuqiang Liu, Xinhua Qu, Zanjing Zhai, Haowei Li, Fengxiang Liu, Qiming Fan, Tingting Tang, An Qin, Zhenan Zhu
• Journal: Biochemical pharmacology (Biochem Pharmacol) Vol. 93 Issue 1 Pg. 59-71 (Jan 01 2015) ISSN: 1873-2968 [Electronic] England
• PMID: 25449599 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Flavonoids
• RANK Ligand
• Tnfsf11 protein, mouse
• myricetin
• Titanium

Topics

• Animals
• Cells, Cultured
• Dose-Response Relationship, Drug
• Flavonoids (pharmacology, therapeutic use)
• Male
• Mice
• Mice, Inbred C57BL
• Osteoclasts (drug effects, pathology)
• Osteolysis (chemically induced, pathology, prevention & control)
• Particle Size
• RANK Ligand (antagonists & inhibitors, pharmacology)
• Random Allocation
• Titanium (toxicity)