Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway

  • Drug Des Devel Ther. 2021 Nov 23;15:4741-4757. doi: 10.2147/DDDT.S334421.
Xinhui Wu   #  1  2 ,  Kangxian Zhao   #  1  2 ,  Xiaoxin Fang  3  4 ,  Feng Lu  3  4 ,  Weikang Zhang  1  2 ,  Xiaoting Song  1  2 ,  Lihua Chen  5 ,  Jiacheng Sun  1  2 ,  Haixiao Chen  1  2  4
Affiliations
  • 1. Wenzhou Medical University, Wenzhou, People's Republic of China.
  • 2. Department of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People's Republic of China.
  • 3. Zhejiang University School of Medicine, Hangzhou, People's Republic of China.
  • 4. Taizhou Hospital of Zhejiang Province, Zhejiang University, Linhai, People's Republic of China.
  • 5. Enze Medical Research Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People's Republic of China.
  • # Contributed equally.
PMID: 34848946 DOI: 10.2147/DDDT.S334421
Abstract

Background: Osteolytic diseases such as osteoporosis are featured with accelerated osteoclast differentiation and strong bone resorption. Considering the complications and Other limitations of current drug treatments, it is necessary to develop a safer and more reliable drug to deal with osteoclast-related diseases. Saikosaponin D (SSD) is the active extract of Bupleurum, which has anti-inflammation, anti-tumor and liver protection functions. However, the role of SSD in regulating the differentiation and function of osteoclasts is not clear.

Purpose: To explore whether SSD could prevent osteoclast differentiation and bone resorption induced by M-CSF and RANKL, and further evaluate the potential therapeutic properties of SSD in LPS-induced inflammatory bone loss mouse models.

Methods: BMMs were cultured in complete medium stimulated by RANKL with different concentrations of SSD. TRAP staining, bone resorption determination, qRT-PCR, immunofluorescence and Western blotting were performed. A mouse model of LPS-induced calvarial bone loss was established and treated with different doses of SSD. The excised calvaria bones were used for TRAP staining, micro-CT scan and histological analysis.

Results: SSD inhibited the formation and bone resorption of osteoclasts induced by RANKL in vitro. SSD suppressed LPS-induced inflammatory bone loss in vivo.

Conclusion: SSD inhibited osteoclastogenesis and LPS-induced osteolysis in mice both which served as a new potential agent for the treatment of osteoclast-related conditions.

Keywords
MAPKs; NF-κB; PI3K-AKT; osteoclastogenesis; saikosaponin D; therapy.
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