Sarsasapogenin Suppresses RANKL-Induced Osteoclastogenesis in vitro and Prevents Lipopolysaccharide-Induced Bone Loss in vivo

• Published in: Drug design, development and therapy development and therapy, 2020-01, Vol.14, p.3435-3447
• Main Authors: Peng, Jiaxuan, Zhao, Kangxian, Zhu, Jiling, Wang, Yanben, Sun, Peng, Yang, Qichang, Zhang, Tan, Han, Weiqi, Hu, Wenjun, Yang, Wanlei, Ruan, Jianwei, Qian, Yu
• Format: Article
• Language: English
• Subjects: Animals; Anticancer properties; Antitumor activity; Biomedical materials; Bone loss; Bone marrow; Bone resorption; Cancer; Cells, Cultured; Diseases; Dose-Response Relationship, Drug; Drug dosages; Ligands; Lipopolysaccharides; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Male; MAP kinase; mapk; Medical treatment; Mice; Mice, Inbred C57BL; Molecular Conformation; nf-κb; NF-κB protein; nfatc1; Original Research; osteoclast; Osteoclastogenesis; Osteoclasts; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteoclasts - pathology; Osteogenesis - drug effects; Osteolysis; Osteolysis - pathology; Osteolysis - prevention & control; Osteoporosis; Penicillin; Phosphatase; RANK Ligand - antagonists & inhibitors; RANK Ligand - metabolism; Sarsasapogenin; Scanning electron microscopy; Signaling; Spirostans - chemistry; Spirostans - pharmacology; Stains & staining; Structure-Activity Relationship; therapeutics; TRANCE protein
• ISSN: 1177-8881; 1177-8881
• DOI: 10.2147/DDDT.S256867

Osteoclasts are giant polynuclear cells; their main function is bone resorption. An increased number of osteoclasts and enhanced bone resorption exert significant effects on osteoclast-related bone-lytic diseases, including osteoporosis. Given the limitations of current therapies for osteolytic diseases, it is urgently required to develop safer and more effective alternatives. Sarsasapogenin, a major sapogenin from Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear. We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts. Sarsasapogenin inhibited multiple RANKL-induced signaling cascades, thereby inhibiting the induction of key osteoclast transcription factor NFATc1. The in vivo and in vitro results were consistent: sarsasapogenin treatment protected against bone loss in a mouse osteolysis model induced by lipopolysaccharide. Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.