The therapeutic effect of Fufang Zhenshu Tiaozhi (FTZ) on osteoclastogenesis and ovariectomized-induced bone loss: evidence from network pharmacology, molecular docking and experimental validation
机构：[1]School of Molecular Sciences, University of Western Australia, Perth 6009, Western Australia, Australia.[2]Department of Endocrinology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, Guangdong, China.[3]College of Food and Medicine, Qingyuan Polytechnic, Qingyuan 511510, Guangdong, China.[4]Department of Orthopedic, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, Guangdong, China.[5]Department of Orthopedic, Yunfu Hospital of Traditional Chinese Medicine, Yunfu 527300, Guangdong, China.[6]Department of Stomatology, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, Guangdong, China.[7]School of Biomedical Sciences, University of Western Australia, Perth 6009, Western Australia, Australia.
Fufang Zhenshu Tiaozhi (FTZ) has been widely used in clinical practice and proven to be effective against aging-induced osteoporosis in mice. This study aimed to explore the mechanism of FTZ against osteoclastogenesis and ovariectomized-induced (OVX) bone loss through the network pharmacology approach. The ingredients of FTZ were collected from the previous UPLC results, and their putative targets were obtained through multiple databases. Differentially expressed genes (DEGs) during osteoclastogenesis were identified through multi-microarrays analysis. The common genes between FTZ targets and DEGs were used to perform enrichment analyses through the clusterProfier package. The affinity between all FTZ compounds and enriched genes was validated by molecular docking. The effects of FTZ on osteoclastogenesis and bone resorption were evaluated by TRAP staining, bone resorption assay and RT-qPCR in vitro, while its effects on bone loss by ELISA and Micro-CT in vivo. Enrichment analyses indicated that the inhibitory effects of FTZ may primarily involve the regulation of inflammation, osteoclastogenesis, as well as TNF-α signaling pathway. 130 pairs docking results confirmed FTZ ingredients have good binding activities with TNF-α pathway enriched genes. FTZ treatment significantly reduced TRAP, TNF-α, IL-6 serum levels and increased bone volume in OVX mice. Consistently, in vitro experiments revealed that FTZ-containing serum significantly inhibited osteoclast differentiation, bone resorption, and osteoclast related mRNA expression. This study revealed the candidate targets of FTZ and its potential mechanism in inhibiting osteoclastogenesis and bone loss induced by OVX, which will pave the way for the application of FTZ in the postmenopausal osteoporosis treatment.
基金：
National Science Foundation for Young Scholars, China [No. 81603641], Science and Technology Planning Project of Yunfu, Guangdong Province, China [No. 2020A090402] and Administration of Traditional Chinese Medicine of Guangdong Province, China [No. 20222120].
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外文
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出版当年[2021]版：
大类|3 区医学
小类|3 区细胞生物学3 区老年医学
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第一作者机构：[1]School of Molecular Sciences, University of Western Australia, Perth 6009, Western Australia, Australia.
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推荐引用方式(GB/T 7714)：
Chen Xiaojun,Wang Jiangyan,Tang Lin,et al.The therapeutic effect of Fufang Zhenshu Tiaozhi (FTZ) on osteoclastogenesis and ovariectomized-induced bone loss: evidence from network pharmacology, molecular docking and experimental validation[J].Aging.2022,14(undefined):doi:10.18632/aging.204172.
APA：
Chen Xiaojun,Wang Jiangyan,Tang Lin,Ye Qiuying,Dong Qunwei...&Sun Ping.(2022).The therapeutic effect of Fufang Zhenshu Tiaozhi (FTZ) on osteoclastogenesis and ovariectomized-induced bone loss: evidence from network pharmacology, molecular docking and experimental validation.Aging,14,(undefined)
MLA：
Chen Xiaojun,et al."The therapeutic effect of Fufang Zhenshu Tiaozhi (FTZ) on osteoclastogenesis and ovariectomized-induced bone loss: evidence from network pharmacology, molecular docking and experimental validation".Aging 14..undefined(2022)
