Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-қB activation and titanium particle-induced osteolysis in a mouse model
| Autor: | Ren-Xiang Tan, Jianbin Huang, Jiming Ye, Estabelle S.M. Ang, Nathan J. Pavlos, Qian Liu, Yue Ding, Jun Xu, Jiake Xu, Haotian Feng, Huafei Wu, Lin Zhou, Shek Man Chim, Jinmin Zhao, Wei Xue, Jennifer Tickner |
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| Rok vydání: | 2015 |
| Předmět: |
musculoskeletal diseases
Osteolysis Osteoclasts Biochemistry Bone resorption Cell Line Mice chemistry.chemical_compound Endocrinology Osteoclast medicine Animals Antineoplastic Agents Alkylating Molecular Biology Titanium biology RANK Ligand Transcription Factor RelA NF-κB Phenanthrenes Triptolide medicine.disease Resorption medicine.anatomical_structure chemistry RANKL Immunology Cancer research biology.protein Epoxy Compounds Diterpenes |
| Zdroj: | Molecular and Cellular Endocrinology. 399:346-353 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2014.10.016 |
| Popis: | The RANKL-induced NF-κB signaling pathway is required for osteoclast formation and function. By screening for compounds that inhibit RANKL-induced NF-κB activation using a luciferase reporter gene assay in RAW264.7 cells, we identified triptolide (PG490), as a candidate compound targeting osteoclast differentiation and osteoclast-mediated osteolysis. Triptolide (PG490) is an active compound of the medicinal herb Tripterygium wilfordii Hook F (TWHF) or Lei Gong Teng with known anti-inflammatory properties. We found that triptolide inhibited osteoclastogenesis and bone resorption, as well as RANKL-induced NF-қB activities as monitored by luciferase reporter gene assays and the nuclear translocation of p65. In vivo studies showed that triptolide attenuates titanium-induced osteolysis and osteoclast formation in a mouse calvarial model. Considering that drugs which protect against localized bone loss are critically needed for the effective treatment of particle-induced osteolysis, our data suggest that triptolide might have therapeutic potential for the treatment of bone lytic diseases caused by prosthetic wear particles. |
| Databáze: | OpenAIRE |
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