Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation

Kong, Xiangying; Wu, Wenbin; Yang, Yanqi; Wan, Heng; Li, Xiaomin; Zhong, Michun; Zhao, Hongyan; Su, Xiaohui; Jia, Shiwei; Ju, Dianwen; Lin, Na

doi:10.1186/s12967-015-0440-1

Cited by 21 publications

(18 citation statements)

References 41 publications

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“…The RANKL-RANK interaction results in the phosphorylation of MAPKs, including JNK, p38 and ERK, promoting the activation of c-Fos and facilitating the translocation of activator protein-1, an essential translation factor for osteoclast formation. Previous studies have confirmed that inhibitors of p38, JNK or ERK inhibit osteoclast formation (46,47). In the present study, ZOL diminished the phosphorylation of JNK induced by RANKL.…”

Section: Discussionmentioning

confidence: 67%

Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways

Huang

Cheng

et al. 2019

Int J Mol Med

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It is well known that extensive osteoclast formation plays a key role in osteoporosis in post-menopausal women and the elderly. The suppression of extensive osteoclastogenesis and bone resorption may be an effective preventive strategy for osteoporosis. Zoledronic acid (ZOL) has been indicated to play an essential role in regulating bone mineral density and has already been used in large clinical trials. However, the effects of ZOL on osteoclastogenesis remain to be fully elucidated. Therefore, the present study aimed to determine the effects of ZOL on osteoclastogenesis, and to explore the corresponding signalling pathways. By using a cell viability assay, as well as in vitro osteoclastogenesis, immunofluorescence and resorption pit assays, we demonstrated that ZOL (0.1-5 µ M) suppressed receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and bone resorptive activity. Furthermore, western blot analysis and reverse transcription-quantitative PCR indicated that ZOL inhibited the RANKL-induced activation of NF-κB and the phosphorylation of JNK in RAW264.7 cells, and subsequently decreased the expression of osteoclastogenesis-associated genes, including calcitonin receptor, tartrate-resistant acid phosphatase and dendritic cell-specific transmembrane protein. ZOL inhibited osteoclast formation and resorption in vitro by specifically suppressing NF-κB and JNK signalling. On the whole, the findings of this study indicate that ZOL may serve as a potential agent for the treatment of osteoclast-associated diseases, including osteoporosis.

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Section: Discussionmentioning

confidence: 67%

Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways

Huang

Cheng

et al. 2019

Int J Mol Med

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“…Osteoclasts are bone-specialized multinucleated cells and are responsible for bone-destructive diseases, such as rheumatoid arthritis and osteoporosis. In RAW264.7 cells and CIA rats, the total saponin (TS) of A. flaccida concentration-dependently inhibited receptor activator of NF- κ B ligand (RANKL)-induced osteoclast formation and bone marrow-derived macrophages (BMMs), as well as decreased extent of actin ring formation and lacunar resorption 6 , 37 . The RANKL-stimulated expression of osteoclast-related transcription factors was also diminished by TS, while the expression of osteoprotegerin (OPG), at both mRNA and protein levels increased, and the ratio of RANKL to OPG in inflamed joints and sera of CIA rats decreased 37 .…”

Section: Bioactivitiesmentioning

confidence: 99%

“…The state-of-the-art methods have been adopted to isolate bioactive chemical constituents from Anemone species following bioactivity-directed fractionation 4 , 5 . Some modes of action of bioactive extracts or compounds of Anemone species have been established 6 , 7 . However, a comprehensive review of the Anemone medicinal resources is lacking.…”

Section: Introductionmentioning

confidence: 99%

Anemone medicinal plants: ethnopharmacology, phytochemistry and biology

Hao

Xiao

2017

Acta Pharmaceutica Sinica B

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The Ranunculaceae genus Anemone (order Ranunculales), comprising more than 150 species, mostly herbs, has long been used in folk medicine and worldwide ethnomedicine. Various medicinal compounds have been found in Anemone plants, especially triterpenoid saponins, some of which have shown anti-cancer activities. Some Anemone compounds and extracts display immunomodulatory, anti-inflammatory, antioxidant, and antimicrobial activities. More than 50 species have ethnopharmacological uses, which provide clues for modern drug discovery. Anemone compounds exert anticancer and other bioactivities via multiple pathways. However, a comprehensive review of the Anemone medicinal resources is lacking. We here summarize the ethnomedical knowledge and recent progress on the chemical and pharmacological diversity of Anemone medicinal plants, as well as the emerging molecular mechanisms and functions of these medicinal compounds. The phylogenetic relationships of Anemone species were reconstructed based on nuclear ITS and chloroplast markers. The molecular phylogeny is largely congruent with the morphology-based classification. Commonly used medicinal herbs are distributed in each subgenus and section, and chemical and biological studies of more unexplored taxa are warranted. Gene expression profiling and relevant “omics” platforms could reveal differential effects of phytometabolites. Genomics, transcriptomics, proteomics, and metabolomics should be highlighted in deciphering novel therapeutic mechanisms and utilities of Anemone phytometabolites.

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“…TRAF6 is closely associated with the maturation and differentiation of osteoclasts in vitro (20). Recent studies have reported that TRAF6 serves an important role in the development, invasion and metastasis of tumors by activating nuclear factor (NF)-κb (21,22). however, studies regarding the expression of TRAF6 in osteosarcoma and its biological role are rare.…”

Section: The Effects Of Traf6 On Proliferation Apoptosis and Invasiomentioning

confidence: 99%

The effects of TRAF6 on proliferation, apoptosis and invasion in osteosarcoma are regulated by miR-124

Meng

Zhang

et al. 2018

Int J Mol Med

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The present study aimed to verify tumor necrosis factor receptor‑associated factor 6 (TRAF6) as the target gene of microRNA-124 (miR-124). In addition, the expression of miR‑124 was investigated in osteosarcoma tissues and cells, and its effects on the biological characteristics of osteosarcoma cells were determined, in order to provide an experimental and theoretical basis for the application of TRAF6 in the treatment of osteosarcoma. A fluorescence reporter enzyme system was used to verify TRAF6 as a target gene of miR‑124, and western blotting was used to detect the effects of miR‑124 on the protein expression levels of TRAF6 in cells. The expression levels of miR‑124 were detected in osteosarcoma tissues and an osteosarcoma cell line (MG‑63) by quantitative polymerase chain reaction (qPCR). In addition, a total of 48 h post‑transfection of MG‑63 cells with a miR‑124 mimic, qPCR was used to detect the expression levels of miR‑124, and the effects of miR‑124 on the viability of MG‑63 human osteosarcoma cells was determined using the MTT method. The effects of miR‑124 on the cell cycle progression and apoptosis of MG‑63 cells were analyzed by flow cytometry, whereas the effects of miR‑124 on the migration of MG‑63 cells was detected using the Transwell invasion chamber analysis method. A TRAF6 recombinant expression plasmid (pcDNA3.1‑TRAF6) was also constructed, and MG‑63 cells were transfected with the recombinant plasmid and a miR‑124 mimic, in order to further validate the biological role of miR‑124 via the regulation of TRAF6. The results of the present study indicated that, compared with in the normal control group, the expression levels of miR‑124 were significantly increased in MG‑63 cells transfected with a miR‑124 mimic (P<0.01). In addition, the luciferase reporter gene system demonstrated that, compared with in the control group, relative luciferase activity was significantly reduced in the miR‑124 mimic group (P<0.01). The results of MTT analysis indicated that cell viability was also significantly reduced in response to the overexpression of miR‑124 in MG‑63 cells (P<0.01). Flow cytometric analysis demonstrated that the proportion of cells in S phase and G2/M phase was significantly decreased (P<0.01) in cells overexpressing miR‑124, and the number of apoptotic cells was significantly increased (P<0.01). Furthermore, the results of the Transwell invasion assay suggested that the number of invasive cells was significantly decreased following enhanced expression of miR‑124 (P<0.01). In MG‑63 cells overexpressing miR‑124 and TRAF6, the results of MTT, flow cytometric and Transwell assay analyses demonstrated that the overexpression of TRAF6 had the opposite biological effects compared to miR‑124 overexpression. In conclusion, the present study indicated that the expression levels of miR‑124 were downregulated in human osteosarcoma tissues and cells, and that miR‑124 is associated with negative regulation of TRAF6 expression; therefore, the role of TRAF6 in primary osteosarcoma may be regulated by miR‑1...

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Total saponin from Anemone flaccida Fr. Schmidt abrogates osteoclast differentiation and bone resorption via the inhibition of RANKL-induced NF-κB, JNK and p38 MAPKs activation

Cited by 21 publications

References 41 publications

Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways

Zoledronic acid inhibits osteoclast differentiation and function through the regulation of NF-κB and JNK signalling pathways

Anemone medicinal plants: ethnopharmacology, phytochemistry and biology

The effects of TRAF6 on proliferation, apoptosis and invasion in osteosarcoma are regulated by miR-124

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