Natural Germacrane Sesquiterpenes Inhibit Osteoclast Formation, Bone Resorption, RANKL-Induced NF-κB Activation, and IκBα Degradation

International Journal of Molecular Sciences

Shengnan Qin⁶  Estabelle Ang⁴  Libing Dai⁶  Xiaohong Yang⁶  Dongping Ye⁶  Honghui Chen⁶  Lin Zhou²  Mingli Yang²  Dian Teguh²  Renxiang Tan⁷  Jun Xu⁵  Jennifer Tickner²  Nathan J. Pavlos³  Jiake Xu⁶  Ge Zhang¹ 

[1] Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, ChinaSchool 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, AustraliaSchool of Dentistry, University of Western Australia, Perth, WA 6009, Australia;Research Center for Drug Discovery (RCDD), School of Pharmaceutical Sciences, Sun Yat-Sen University, 132 East Circle at University City, Guangzhou 510006, China;Guangzhou Institute of Traumatic Surgery, Guangzhou Red Cross Hospital, Medical College, Jinan University, Guangzhou 510220, China;Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China;

关键词: germacrane sesquiterpenes;    osteoclastogenesis;    bone resorption;    RANKL;    NF-κB;    IκBα;   

DOI  :  10.3390/ijms161125972

来源: mdpi

【 摘 要 】

Osteolytic bone diseases are commonly presented with enhanced osteoclast formation and bone resorption. Sesquiterpene lactone natural compounds have been found to possess anti-inflammatory and immune-modulation effects. Here, we identified three germacrane sesquiterpenes using computer-based virtual screening for the structural similarity with sesquiterpene lactone, parthenolide. We showed that natural germacrane sesquiterpene compounds A, B, and C inhibit osteoclast formation and bone resorption in a dose-dependent manner, with relative potency compound A > compound C > compound B based on their equimolar concentrations. Mechanistic studies by Luciferase reporter gene assay and Western blot analysis showed that germacrane sesquiterpene compound A inhibits RANKL-induced activation of NF-κB and IκBα degradation. This study reveals that natural germacrane sesquiterpene compounds are inhibitors for osteoclast formation and bone resorption, and provides evidence that naturally-occurring compounds might be beneficial as alternative medicine for the prevention and treatment of osteolysis.

【 授权许可】

CC BY   
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