1. A natural compound (LCA) isolated from Litsea cubeba inhibits RANKL-induced osteoclast differentiation by suppressing Akt and MAPK pathways in mouse bone marrow macrophages.
- Author
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Yu L, Jia D, Feng K, Sun X, Xu W, Ding L, Xin H, Qin L, and Han T
- Subjects
- Animals, Cells, Cultured, Femur cytology, Lignin isolation & purification, Macrophages enzymology, Male, Mice, Inbred C57BL, Osteoclasts enzymology, Plant Extracts isolation & purification, Signal Transduction, Tibia cytology, Cell Transdifferentiation drug effects, Lignin pharmacology, Litsea chemistry, Macrophages drug effects, Mitogen-Activated Protein Kinases metabolism, Osteoclasts drug effects, Osteogenesis drug effects, Plant Extracts pharmacology, Proto-Oncogene Proteins c-akt metabolism, RANK Ligand pharmacology
- Abstract
Ethnopharmacological Relevance: Litsea cubeba (Lour.) Pers. has been traditionally used as a folk prescription for treating rheumatic diseases in China., Aim of the Study: This study aimed to investigate the effects and underlying mechanism of LCA, a new type of dibenzyl butane lignin compound extracted from L. cubeba, on macrophage colony stimulating factor (M-CSF) plus receptor activator of NF-κB ligand (RANKL)-induced osteoclast differentiation in mouse-derived bone marrow macrophages (BMMs)., Material and Methods: TRAP staining, TRAP enzyme activity assay and actin ring staining were applied to identify the effects of LCA on osteoclast differentiation. Protein expression of NFATc1, c-Fos and MMP-9, and phosphorylation of p65, Akt, JNK, ERK and p38 in RANKL-induced osteoclasts was determined using western blotting to investigate the underlying mechanism., Results: LCA significantly suppressed RANKL-induced osteoclast differentiation by inhibiting TRAP activity, decreasing the number of TRAP
+ multinuclear osteoclasts and reducing the formation of F-actin ring without obvious cytotoxicity in BMMs. Moreover, LCA treatment strongly reduced protein expression of NFATc1, c-Fos and MMP-9, and attenuated the phosphorylation of p65, Akt, JNK, ERK and p38 in RANKL-stimulated BMMs., Conclusions: LCA ameliorated RANKL-induced osteoclast differentiation via inhibition of Akt and MAPK signalings in BMMs, and may serve as a potential pro-drug for bone destruction prevention., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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