1. Vaccaria hypaphorine impairs RANKL-induced osteoclastogenesis by inhibition of ERK, p38, JNK and NF-κB pathway and prevents inflammatory bone loss in mice.
- Author
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Chen H, Guo T, Wang D, and Qin R
- Subjects
- Animals, Anti-Inflammatory Agents administration & dosage, Anti-Inflammatory Agents isolation & purification, Anti-Inflammatory Agents pharmacology, Bone Resorption drug therapy, Cell Differentiation drug effects, Dose-Response Relationship, Drug, Lipopolysaccharides, Male, Mice, Mice, Inbred C57BL, Plant Extracts administration & dosage, RANK Ligand administration & dosage, RANK Ligand metabolism, RAW 264.7 Cells, Osteoclasts drug effects, Osteogenesis drug effects, Plant Extracts pharmacology, Vaccaria chemistry
- Abstract
Osteoclasts are sole bone-resorbing cells which exert a profound effect on skeletal metabolism. The search for medicines that affect the differentiation and function of osteoclasts is crucial in developing therapies for osteoclast-based diseases. Vaccaria hypaphorine, the main active compound of the traditionally used Chinese herb Vaccaria segetalis, has anti-inflammatory activity. The present study demonstrated for the first time that vaccaria hypaphorine could significantly inhibit the receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastic differentiation in vitro and alleviate lipopolysaccharide (LPS)-induced bone loss in vivo. Further study showed that vaccaria hypaphorine decreased osteoclastogenesis in a dose-dependent manner. Furthermore, vaccaria hypaphorine was confirmed to inhibit osteoclasts differentiation at early stage but not at later stage. Pit formation assay and F-actin ring staining showed that vaccaria hypaphorine inhibited the bone-resorbing activity of osteoclasts. Mechanistically, vaccaria hypaphorine impaired RANKL-induced osteoclastogenesis through reduction of extracellular signal-regulated kinases (ERK), p38, c-Jun N-terminal kinase (JNK) and NF-κB p65 phosphorylation. Taken together, our results provided evidences that vaccaria hypaphorine might be considered as potential therapeutic agent for treating osteoclast-based bone loss., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)
- Published
- 2018
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