Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 399, Issue C, Pages 346-353Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2014.10.016
Keywords
Triptolide; Osteoclastogenesis; RANKL; NF-kappa B; Osteolysis; Titanium particle
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Funding
- National Health and Medical Research Council of Australia [1010420]
- Arthritis Foundation of Western Australia
- University of Western Australia Research Collaboration Awards
- National Natural Science Foundation of China [81272020, 81228013]
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The RANKL-induced NF-kappa B signaling pathway is required for osteoclast formation and function. By screening for compounds that inhibit RANKL-induced NF-kappa B 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-kappa B 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. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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