A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

Zhi, Xiao; Cui, Jin; Liu, Chao; Zheng, Zhaohui; Cao, Liehu; Pan, Panpan; Weng, Weizong; Zhai, Xiaofeng; Zhao, Qingjie; Hu, Honggang; Qin, Longjuan; Chen, Xiao; Su, Jiacan

doi:10.3389/fphar.2018.00022

Cited by 29 publications

(28 citation statements)

References 43 publications

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“…Each group consists six mice. The OVX surgery were carried out as described in our former study 24. The mice in Trip group were intraperitoneally (i.p.)…”

Section: Methodsmentioning

confidence: 99%

Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K‐AKT‐NFATc1 pathway

Cui

Wang

et al. 2020

J Cellular Molecular Medi

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Bone loss (osteopenia) is a common complication in human solid tumour. In addition, after surgical treatment of gynaecological tumour, osteoporosis often occurs due to the withdrawal of oestrogen. The major characteristic of osteoporosis is the low bone mass with micro‐architectural deteriorated bone tissue. And the main cause is the overactivation of osteoclastogenesis, which is one of the most important therapeutic targets. Inflammation could induce the interaction of RANKL/RANK, which is the promoter of osteoclastogenesis. Triptolide is derived from the traditional Chinese herb lei gong teng, presented multiple biological effects, including anti‐cancer, anti‐inflammation and immunosuppression. We hypothesized that triptolide could inhibits osteoclastogenesis by suppressing inflammation activation. In this study, we confirmed that triptolide could suppress RANKL‐induced osteoclastogenesis in bone marrow mononuclear cells (BMMCs) and RAW264.7 cells and inhibited the osteoclast bone resorption functions. PI3K‐AKT‐NFATc1 pathway is one of the most important downstream pathways of RANKL‐induced osteogenesis. The experiments in vitro indicated that triptolide suppresses the activation of PI3K‐AKT‐NFATc1 pathway and the target point located at the upstream of AKT because both NFATc1 overexpression and AKT phosphorylation could ameliorate the triptolide suppression effects. The expression of MDM2 was elevated, which demonstrated the MDM‐p53‐induced cell death might contribute to the osteoclastogenesis suppression. Ovariectomy‐induced bone loss and inflammation activation were also found to be ameliorated in the experiments in vivo. In summary, the new effect of anti‐cancer drug triptolide was demonstrated to be anti‐osteoclastogenesis, and we demonstrated triptolide might be a promising therapy for bone loss caused by tumour.

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“…Each group consists six mice. The OVX surgery were carried out as described in our former study 24. The mice in Trip group were intraperitoneally (i.p.)…”

Section: Methodsmentioning

confidence: 99%

Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K‐AKT‐NFATc1 pathway

Cui

Wang

et al. 2020

J Cellular Molecular Medi

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“…NFATc1 plays a vital role in osteoclast maturation and activation via upregulating the gene expression of osteoclastic-related genes including matrix metalloproteinase (Mmps), Trap, and Cathepsin K (Ctsk) [6][7][8][9]. us, targeting osteoclast formation and differentiation via inhibiting NF-κB and MAPK signaling are an effective strategy toward preventing bone loss related diseases [10,11].…”

Section: Introductionmentioning

confidence: 99%

The Coumarin Derivative 5′-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways

Abdallah

Ali

Badr

et al. 2019

BioMed Research International

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e phytochemical substances, coumarin derivatives, have demonstrated antiresorptive bone effects by suppressing osteoclast differentiation in vitro and in vivo. Recently, we have identified 5′-hydroxy auraptene (5′-HA), a coumarin derivative isolated from Lotus lalambensis Schweinf, as a novel stimulator for osteoblast differentiation. In this study, we investigated the effect of 5′-HA on osteoclast differentiation of mouse bone marrow (BM) cells. e effect of 5′-HA on BM cell proliferation and osteoclast differentiation was determined by measuring cell viability and tartrate-resistant acid phosphatase (TRAP) enzyme activity, quantification of TRAP + multinucleated cells (TRAP + MNCs), and quantitative real-time PCR (qPCR) of osteoclastic gene expression. Regulation of NF-κB, c-Fos/NFATc1, and MAPK signaling pathways by 5′-HA during osteoclastogenesis was measured by the NF-κB reporter assay and Western blot analysis. 5′-HA significantly suppresses the receptor activator of NF-κB ligand (RANKL) induced osteoclast differentiation of BM cells in a dose-dependent manner. Consistently, treatment of BM cells with 5′-HA significantly inhibited RANKL-induced activation of NF-κB and c-Fos/NFATc1 pathways in a dose-dependent manner. Furthermore, RANKL-induced phosphorylation of ERK1/2, p-38, and JNK was significantly inhibited by 5′-HA in BM cells. In conclusion, we identified 5′-HA as a novel coumarin derivative that suppresses RANKL-induced osteoclastogenesis via inhibiting c-Fos/NFATc1 and MAPK signaling pathways.

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“…It is worthwhile to note that RPS5 has been demonstrated to possess important other extra-ribosomal functions including apoptosis and signal transduction (Vizirianakis et al, 1999;Li et al, 2006;Xu et al, 2016;Zhi et al, 2018). The caspaserecruitment domain (CARD) is found in RPS5, which is known to play an important role in apoptosis and inflammation as an essential protein-protein interaction domains (Wilson et al, 1985;Li et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Roles of EvpP in Edwardsiella piscicida-Macrophage Interactions

Qin¹,

Wang²,

Gao³

et al. 2020

Front. Cell. Infect. Microbiol.

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Edwardsiella piscicida is found to be an important facultative intracellular pathogen with a broad host range. These organisms can replicate and survive within host macrophages to escape from the subversion of the immune defense. E. piscicida-macrophage interaction is very important in determining the outcome of edwardsiellasis. As an effector protein of E. piscicida T6SS, EvpP has been determined to be a very important virulence factor for E. piscicida, although its precise role in E. piscicida-macrophage interactions is not yet clear. In this study, the roles of EvpP in E. piscicida-macrophage interactions were characterized. Here, we constructed the deletion mutants of evpP (evpP) and complementation (evpP-C) by the allelic exchange method. Compared to wild type strain (WT), evpP was found to be attenuated for growth within macrophages. In line with this observation, we found its survival capacity was lower than WT under oxidative and acid stress in vitro, which simulate conditions encountered in host macrophages. Attenuation of evpP also correlated with enhanced activation of macrophages, as reflected by augmented NO production in evpP-treated macrophages. Moreover, compared to WT, evpP induced markedly increased apoptosis of macrophages, characterized by increased Annexin V binding and the activation of cleaved caspase-3. These findings provided strong evidence that EvpP is involved in the process of E. piscicida-macrophage interactions and is required for its survival and replication in macrophages. Thus, we propose that EvpP might be an important factor that controlling the fate of E. piscicida inside macrophages. To further exploring the underlying mechanism of EvpP action, the cDNA library was constructed from E. piscicida-infected macrophages and a yeast two-hybrid screen was performed to search for cellular proteins interacting with EvpP. Ribosomal protein S5 (RPS5) was identified as a target of EvpP. Furthermore, the interaction was validated with co-immunoprecipitation assay. This result implies that the observed effect of EvpP on macrophages might be related to RPS5-mediated regulation, contributing to a better understanding of the mechanisms of EvpP involved in E. piscicida-macrophage interactions.

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A Matrine Derivative M54 Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Targeting Ribosomal Protein S5

Cited by 29 publications

References 43 publications

Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K‐AKT‐NFATc1 pathway

Triptolide prevents bone loss via suppressing osteoclastogenesis through inhibiting PI3K‐AKT‐NFATc1 pathway

The Coumarin Derivative 5′-Hydroxy Auraptene Suppresses Osteoclast Differentiation via Inhibiting MAPK and c-Fos/NFATc1 Pathways

Roles of EvpP in Edwardsiella piscicida-Macrophage Interactions

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