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

  • Drug Des Devel Ther. 2020 Aug 24;14:3435-3447. doi: 10.2147/DDDT.S256867.
Jiaxuan Peng   #  1 ,  Kangxian Zhao   #  2 ,  Jiling Zhu   #  3 ,  Yanben Wang  4  5 ,  Peng Sun  2 ,  Qichang Yang  2 ,  Tan Zhang  4 ,  Weiqi Han  4 ,  Wenjun Hu  4 ,  Wanlei Yang  4 ,  Jianwei Ruan  6 ,  Yu Qian  1  2  4
Affiliations
  • 1. Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, People's Republic of China.
  • 2. The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, People's Republic of China.
  • 3. Department of Clinical Medicine, Medical College of Shaoxing University, Shaoxing, Zhejiang 312000, People's Republic of China.
  • 4. Department of Orthopaedics, Shaoxing People's Hospital, Zhejiang University School of Medicine, Shaoxing 312000, Zhejiang, People's Republic of China.
  • 5. Department of Orthopaedics, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, People's Republic of China.
  • 6. Department of Orthopaedics, Taizhou Municipal Hospital, Taizhou 318000, Zhejiang, Republic of China.
  • # Contributed equally.
PMID: 32943842 DOI: 10.2147/DDDT.S256867
Abstract

Introduction: 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 Anemarrhena asphodeloides Bunge, possesses potent antitumor effects and inhibits NF-κB and MAPK signaling. However, the manner in which it affects osteoclasts is unclear.

Methods: We investigated the effects of anti-osteoclastogenic and anti-resorptive of sarsasapogenin on bone marrow-derived osteoclasts.

Results: 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.

Conclusion: Our research confirms that sarsasapogenin can be used as a new treatment for osteoclast-related osteolytic diseases.

Keywords
MAPK; NF-κB; NFATc1; osteoclast; osteoclastogenesis; sarsasapogenin; therapeutics.
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