title: Gambogic acid inhibits osteoclast formation and ovariectomy-induced osteoporosis by suppressing the JNK, p38 and Akt signalling pathways.
abstract: Excessive osteoclast formation and bone resorption are key causes of osteoporosis. Natural compounds can serve as alternative therapeutic agents for the prevention and treatment of osteoporosis, and some natural compounds may have advantages over traditional drugs. In the present paper, we report that the natural compound GBA (gambogic acid), which is bioavailable, effective and less toxic, inhibits osteoclast formation, thereby attenuating osteoclastic bone resorption in vitro. Further in vivo studies demonstrated that GBA prevented ovariectomy-induced bone loss in a dose-dependent manner. Moreover, we demonstrated that GBA suppressed RANKL (receptor activator of nuclear factor κB ligand)-induced JNK (c-Jun N-terminal kinase), p38 and Akt phosphorylation. Taken together, our results demonstrate that GBA inhibits osteoclast formation in vitro and in vivo, suggesting that it is of potential value in the treatment of osteoclast-related diseases.
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People's Republic of China Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou 310016, People's Republic of China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People's Republic of China Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou 310016, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Ma
authors.affiliation: Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, People's Republic of China.
authors.forename: Xuqiang
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People's Republic of China Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou 310016, People's Republic of China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People's Republic of China Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou 310016, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Orthopaedics, Shanghai Key Laboratory of Orthopaedic Implant, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200011, People's Republic of China dr_qinan@163.com orthopaedics2009@hotmail.com.
authors.forename: An
authors.initials: A
authors.lastname: Qin
authors.affiliation: Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou 310016, People's Republic of China Sir Run Run Shaw Institute of Clinical Medicine of Zhejiang University, Hangzhou 310016, People's Republic of China dr_qinan@163.com orthopaedics2009@hotmail.com.
authors.forename: Shunwu
authors.initials: S
authors.lastname: Fan
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D015536:Down-Regulation; D005260:Female; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D051058:Oncogene Protein v-akt / Q000235:genetics / Q000378:metabolism*; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D010024:Osteoporosis / Q000188:drug therapy* / Q000201:enzymology* / Q000209:etiology / Q000235:genetics; D010052:Ovariectomy / Q000009:adverse effects*; D053245:RANK Ligand / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D044004:Xanthones / Q000008:administration & dosage*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D053245:RANK Ligand; D044004:Xanthones; C052659:gambogic acid; D051058:Oncogene Protein v-akt; D048051:p38 Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4
keywords: Akt; JNK; gambogic acid; osteoclasts; osteoporosis; p38