Artesunate inhibits RANKL‐induced osteoclastogenesis and bone resorption in vitro and prevents LPS‐induced bone loss in vivo
| Autor: | Jiake Xu, Shao Hui Zong, Lin Huang, Yi Ji Su, Xi Xi Lin, Fang Ming Song, Qian Liu, Cheng Ming Wei, Jinmin Zhao |
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| Rok vydání: | 2017 |
| Předmět: |
Lipopolysaccharides
Male 0301 basic medicine Time Factors Physiology Clinical Biochemistry Osteoporosis Artesunate Osteoclasts Arthritis Osteolysis Bone resorption 03 medical and health sciences 0302 clinical medicine Osteogenesis Osteoclast In vivo medicine Animals Bone Resorption Phosphorylation Cells Cultured Dose-Response Relationship Drug biology Chemistry RANK Ligand Transcription Factor RelA X-Ray Microtomography Cell Biology medicine.disease Artemisinins Resorption Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Primary bone Gene Expression Regulation RANKL 030220 oncology & carcinogenesis Proteolysis Cancer research biology.protein I-kappa B Proteins Signal Transduction |
| Zdroj: | Journal of Cellular Physiology. 233:476-485 |
| ISSN: | 1097-4652 0021-9541 |
| DOI: | 10.1002/jcp.25907 |
| Popis: | Osteoclasts are multinuclear giant cells responsible for bone resorption in lytic bone diseases such as osteoporosis, arthritis, periodontitis, and bone tumors. Due to the severe side-effects caused by the currently available drugs, a continuous search for novel bone-protective therapies is essential. Artesunate (Art), the water-soluble derivative of artemisinin has been investigated owing to its anti-malarial properties. However, its effects in osteoclastogenesis have not yet been reported. In this study, Art was shown to inhibit the nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, the mRNA expression of osteoclastic-specific genes, and resorption pit formation in a dose-dependent manner in primary bone marrow-derived macrophages cells (BMMs). Furthermore, Art markedly blocked the RANKL-induced osteoclastogenesis by attenuating the degradation of IκB and phosphorylation of NF-κB p65. Consistent with the in vitro results, Art inhibited lipopolysaccharide (LPS)-induced bone resorption by suppressing the osteoclastogenesis. Together our data demonstrated that Art inhibits RANKL-induced osteoclastogenesis by suppressing the NF-κB signaling pathway and that it is a promising agent for the treatment of osteolytic diseases. |
| Databáze: | OpenAIRE |
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