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Mol Cell Endocrinol. 2015 Jan 5;399:346-53. doi: 10.1016/j.mce.2014.10.016. Epub 2014 Nov 3.

Triptolide inhibits osteoclast formation, bone resorption, RANKL-mediated NF-қB activation and titanium particle-induced osteolysis in a mouse model.

Author information

1
Orthopaedic Department, Memorial Hospital of Sun Yat-sen University, Guangzhou, China.
2
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
3
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia; Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Perth, WA 6009, Australia.
4
Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Perth, WA 6009, Australia.
5
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia; Research Centre for Regenerative Medicine, Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China, 530021.
6
Research Centre for Regenerative Medicine, Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, China, 530021.
7
Key Laboratory of Biomaterials of Guangdong Higher Education Institutes, Department of Biomedical Engineering, Jinan University, Guangzhou, China, 510632.
8
Institute of Functional Biomolecules, Medical School, Nanjing University, Nanjing, China, 210093.
9
Health Innovations Research Institute and School of Health Sciences, RMIT University, Melbourne, VIC 3083, Australia.
10
Research Center for Drug Discovery (RCDD), School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle at University City, Guangzhou, China, 510006.
11
School of Dentistry, University of Western Australia, Perth, WA 6009, Australia.
12
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia; Program of Nutrition and Bone & Joint Health, Nestlé R&D (China) Ltd. Building 5, No. 5 Dijin Road, Haidian District, Beijing, China, 100095.
13
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia. Electronic address: jiake.xu@uwa.edu.au.
14
Orthopaedic Department, Memorial Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: dingyue36@126.com.

Abstract

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.

KEYWORDS:

NF-κB; Osteoclastogenesis; Osteolysis; RANKL; Titanium particle; Triptolide

PMID:
25448849
DOI:
10.1016/j.mce.2014.10.016
[Indexed for MEDLINE]

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