Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway
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 Chen1,2,4 1Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Orthopedics, Taizhou Hospital of Zhejiang Province Aff...
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2021
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oai:doaj.org-article:c0133468a2a8425e8c8ede05ec598b2b2021-11-23T18:43:01ZInhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway1177-8881https://doaj.org/article/c0133468a2a8425e8c8ede05ec598b2b2021-11-01T00:00:00Zhttps://www.dovepress.com/inhibition-of-lipopolysaccharide-induced-inflammatory-bone-loss-by-sai-peer-reviewed-fulltext-article-DDDThttps://doaj.org/toc/1177-8881Xinhui 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 Chen1,2,4 1Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Taizhou Hospital of Zhejiang Province, Zhejiang University, Linhai, People’s Republic of China; 5Enze Medical Research Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haixiao ChenDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, 317000, People’s Republic of ChinaEmail drchx@126.comBackground: 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: saikosaponin D, osteoclastogenesis, NF-κB, MAPKs, PI3K-AKT, therapyWu XZhao KFang XLu FZhang WSong XChen LSun JChen HDove Medical Pressarticlesaikosaponin dosteoclastogenesisnf-κbmapkspi3k-akttherapyTherapeutics. PharmacologyRM1-950ENDrug Design, Development and Therapy, Vol Volume 15, Pp 4741-4757 (2021) |
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saikosaponin d osteoclastogenesis nf-κb mapks pi3k-akt therapy Therapeutics. Pharmacology RM1-950 |
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saikosaponin d osteoclastogenesis nf-κb mapks pi3k-akt therapy Therapeutics. Pharmacology RM1-950 Wu X Zhao K Fang X Lu F Zhang W Song X Chen L Sun J Chen H Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway |
| description |
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 Chen1,2,4 1Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Taizhou Hospital of Zhejiang Province, Zhejiang University, Linhai, People’s Republic of China; 5Enze Medical Research Center, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Haixiao ChenDepartment of Orthopedics, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, 317000, People’s Republic of ChinaEmail drchx@126.comBackground: 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: saikosaponin D, osteoclastogenesis, NF-κB, MAPKs, PI3K-AKT, therapy |
| format |
article |
| author |
Wu X Zhao K Fang X Lu F Zhang W Song X Chen L Sun J Chen H |
| author_facet |
Wu X Zhao K Fang X Lu F Zhang W Song X Chen L Sun J Chen H |
| author_sort |
Wu X |
| title |
Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway |
| title_short |
Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway |
| title_full |
Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway |
| title_fullStr |
Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway |
| title_full_unstemmed |
Inhibition of Lipopolysaccharide-Induced Inflammatory Bone Loss by Saikosaponin D is Associated with Regulation of the RANKL/RANK Pathway |
| title_sort |
inhibition of lipopolysaccharide-induced inflammatory bone loss by saikosaponin d is associated with regulation of the rankl/rank pathway |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/c0133468a2a8425e8c8ede05ec598b2b |
| work_keys_str_mv |
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1718416180004257792 |