The effect of QiangGuYin on osteoporosis through the AKT/mTOR/autophagy signaling pathway mediated by CKIP-1

Yuan, Yifeng; Sun, Jianfang; Zhou, Hang; Wang, Shen; He, Caijian; Chen, Tianpeng; Fang, Mouhao; Li, Shaohua; Kang, Shifa; Huang, Xiaosheng; Tang, Binbin; Liang, Bo; Mao, Yingdelong; Li, Jianyou; Shi, Xiaoyi; Liu, Kang

doi:10.18632/aging.203848

Cited by 14 publications

(6 citation statements)

References 45 publications

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“…Previous clinical studies have shown that QGY is highly effective in treating PMOP ( Shi, Liu, and Li, 2007 ; Shi et al, 2008 , 2017 ; Xiao et al, 2019 ; Li et al, 2021 ; Mao et al, 2021 ; Hui et al, 2022 ). Studies have also shown that QGY promotes bone formation and inhibits bone resorption ( Wu et al, 2008 ; Wang, Wu, and Shi, 2016 ; Yao et al, 2016 ; Liu et al, 2018 ; Yang et al, 2018 ; Huang, Shi, and Deng, 2019 ; Liang et al, 2019 ; Yuan et al, 2022 ). Thus, we studied the effects of SBT, QGY, SBT + QGY, and SBT + EU.…”

Section: Discussionmentioning

confidence: 99%

“…Our previous study found that CKIP-1 regulates bone metabolism ( Liu et al, 2018 ; Yang et al, 2018 ) and that QGY acts as an anti-osteoporosis agent by inhibiting CKIP-1 and Akt binding in osteoblasts, activating the Akt/mTOR signaling pathway, inhibiting cellular autophagy, promoting osteogenic differentiation, and promoting osteoporosis ( Yuan et al, 2022 ). QGY also influences osteoblast differentiation through the Wnt/β-catenin pathway by affecting the expression of related miRNAs in the exostome of osteoclasts ( Tang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

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Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/β-catenin signaling pathway and analysis of active ingredients by molecular docking

Yuan

Wang²,

Zhou³

et al. 2022

Front. Pharmacol.

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Background: Sea buckthorn (SBT) is a traditional Chinese medicine (TCM), rich in calcium, phosphorus, and vitamins, which can potentially prevent and treat osteoporosis. However, no research has been conducted to confirm these hypotheses. QiangGuYin (QGY) is a TCM compound used to treat osteoporosis. There is a need to investigate whether SBT enhances QGY efficacy.Objectives: The aim of this study was to explore whether SBT enhances QGY efficacy by inhibiting CKIP-1 and Notum expression through the Wnt/β-catenin pathway. The study also aimed to explore the active components of SBT.Methods: Experimental animals were divided into control, model, QGY, SBT, SBT + Eucommia ulmoides (EU), and SBT + QGY groups. After treatment, bone morphometric parameters, such as estrogen, PINP, and S-CTX levels, and Notum, CKIP-1, and β-catenin expression were examined. Screening of SBT active components was conducted by molecular docking to obtain small molecules that bind Notum and CKIP-1.Results: The results showed that all the drug groups could elevate the estrogen, PINP, and S-CTX levels, improve femoral bone morphometric parameters, inhibit Notum and CKIP-1 expression, and promote β-catenin expression. The effect of SBT + EU and SBT + QGY was superior to the others. Molecular docking identified that SBT contains seven small molecules (folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin) with potential effects on CKIP-1 and Notum.Conclusion: SBT improves bone morphometric performance in PMOP rats by inhibiting CKIP-1 and Notum expression, increasing estrogen levels, and activating the Wnt/β-catenin signaling pathway. Furthermore, SBT enhances the properties of QGY. Folic acid, rhein, quercetin, kaempferol, mandenol, isorhamnetin, and ent-epicatechin are the most likely active ingredients of SBT. These results provide insight into the pharmacological mechanisms of SBT in treating osteoporosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/β-catenin signaling pathway and analysis of active ingredients by molecular docking

Yuan

Wang²,

Zhou³

et al. 2022

Front. Pharmacol.

Self Cite

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“…Osteoporosis is a systemic bone disease characterized by deterioration of the bone microstructure and decreased bone mass, which leads to increased risk of fractures and bone fragility 78 . An omnigenic model or effect is widely thought to be a reasonable way to explain and understand such complex diseases 23 , 24 , as such a model posits that small changes in hundreds or even thousands of genes can lead to a large outcome (i.e., disease).…”

Section: Discussionmentioning

confidence: 99%

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes

Yuan,

Yu,

Wang

et al. 2024

Cell Discov

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Due to a rapidly aging global population, osteoporosis and the associated risk of bone fractures have become a wide-spread public health problem. However, osteoporosis is very heterogeneous, and the existing standard diagnostic measure is not sufficient to accurately identify all patients at risk of osteoporotic fractures and to guide therapy. Here, we constructed the first prospective multi-omics atlas of the largest osteoporosis cohort to date (longitudinal data from 366 participants at three time points), and also implemented an explainable data-intensive analysis framework (DLSF: Deep Latent Space Fusion) for an omnigenic model based on a multi-modal approach that can capture the multi-modal molecular signatures (M3S) as explicit functional representations of hidden genotypes. Accordingly, through DLSF, we identified two subtypes of the osteoporosis population in Chinese individuals with corresponding molecular phenotypes, i.e., clinical intervention relevant subtypes (CISs), in which bone mineral density benefits response to calcium supplements in 2-year follow-up samples. Many snpGenes associated with these molecular phenotypes reveal diverse candidate biological mechanisms underlying osteoporosis, with xQTL preferences of osteoporosis and its subtypes indicating an omnigenic effect on different biological domains. Finally, these two subtypes were found to have different relevance to prior fracture and different fracture risk according to 4-year follow-up data. Thus, in clinical application, M3S could help us further develop improved diagnostic and treatment strategies for osteoporosis and identify a new composite index for fracture prediction, which were remarkably validated in an independent cohort (166 participants).

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“…AMPK/mTOR signaling pathway is also a classical signaling pathway of autophagy, which not only indirectly regulates the functions of osteoblasts and osteoclasts, but also directly participates in the formation of osteoblast mineralization and osteoclast frill ( 28 ). A study has shown that activation of AKT/mTOR signaling pathway can inhibit autophagy, promote cell differentiation, and ultimately play an anti-osteoporosis role ( 29 ). AMPK is also a recognized autophagy regulator that promotes autophagy by inhibiting phosphorylation activation of its downstream target of rapamycin receptors ( 30 ).…”

Section: Discussionmentioning

confidence: 99%

Zhuanggu Zhitong Capsule alleviates postmenopausal osteoporosis in ovariectomized rats by regulating autophagy through AMPK/mTOR signaling pathway

Men¹,

Huang²,

Xu³

et al. 2022

Ann Transl Med

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Background Postmenopausal osteoporosis (PMOP) is the most common primary osteoporosis, which is prone to fractures and affect the health and quality of life of the elderly and even shorten their lifetime. Traditional Chinese medicine can not only effectively improve osteoporosis and reduce fracture rate, but also have tonifying and analgesic effects. The purpose of this study was to investigate the effects of Zhuanggu Zhitong (ZGZT) Capsule on autophagy related genes and proteins in PMOP rats, so as to elucidate the molecular mechanism of tonifying deficiency and regulating stasis in the treatment of osteoporosis and analgesia. Methods The PMOP rat model was established by bilateral oophorectomy, and then the rats were randomly divided into control group, PMOP group, PMOP + ZGZT group and PMOP + E 2 group. The changes of mechanical pain threshold of rats were detected by von Frey filaments, and the changes of mechanical pain threshold of rats in each group were compared. Computed tomography (CT) and dual-energy X-ray were used to measure the bone mineral density of lumbar bone tissue. Enzyme-linked immunosorbent assay (ELISA) and tartrate-resistant acid phosphatase (TRAP) staining were used to detect inflammatory factors and bone metabolism related indicators. Hematoxylin-eosin (HE) staining was used to observe the tissue morphology of lumbar vertebra tissue. Western blot (WB) and quantitative polymerase chain reaction (qPCR) were used to detect AMPK/mTOR pathway- and autophagy-related factor expression. Results ZGZT can effectively restore the bone mineral density (BMD) of PMOP rats, improve the microstructure of lumbar vertebra of PMOP rats, restore the balance of bone metabolism, promote the expression of AMPK and autophagy related factors, inhibit the expression of mTOR and the release of inflammatory factors, and increase the mechanical pain threshold of PMOP rats, so as to effectively improve osteoporosis and relieving osteoporosis pain in PMOP rats. Conclusions ZGZT affects autophagy by regulating AMPK/mTOR pathway, restores the homeostasis of bone metabolism and inhibits the release of inflammatory factors. Moreover, the regulation of feedback pathways between bone metabolism and inflammatory factors finally plays the role of “bone strengthening” and “pain relieving”. ZGZT may be a new treatment for PMOP and relieving osteoporotic pain.

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The effect of QiangGuYin on osteoporosis through the AKT/mTOR/autophagy signaling pathway mediated by CKIP-1

Cited by 14 publications

References 45 publications

Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/β-catenin signaling pathway and analysis of active ingredients by molecular docking

Exploratory study of sea buckthorn enhancing QiangGuYin efficacy by inhibiting CKIP-1 and Notum activating the Wnt/β-catenin signaling pathway and analysis of active ingredients by molecular docking

Multi-modal molecular determinants of clinically relevant osteoporosis subtypes

Zhuanggu Zhitong Capsule alleviates postmenopausal osteoporosis in ovariectomized rats by regulating autophagy through AMPK/mTOR signaling pathway

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