Sinomenine down-regulates TLR4/TRAF6 expression and attenuates lipopolysaccharide-induced osteoclastogenesis and osteolysis

L. He, H. Duan, X. Li, S. Wang, Y. Zhang, L. Lei, Jiake Xu, S. Liu

    Research output: Contribution to journalArticle

    8 Citations (Scopus)

    Abstract

    © 2016 Elsevier B.V. All rights reserved. Sinomenine (SIN) is an anti-inflammatory and anti-arthritic alkaloid derived from Sinomenioum acutum. Effects of SIN on lipopolysaccharide (LPS)-induced osteolysis have not been reported. Here, we found that SIN reduced LPS-induced erosion of skull bones in C57BL/6 mice significantly. LPS can induce bone-absorbing osteoclast formation independent of RANKL in pre-osteoclastic RAW264.7 cells in vitro. Here, SIN suppressed LPS-induced osteoclast formation and osteoclast survival in RAW264.7 cells. Expression of osteoclastic-specific marker genes was also inhibited by SIN during osteoclast differentiation and osteoclast survival stimulated with LPS. SIN showed much stronger inhibitory effects on expression of Fra-1 and MMP-9 mRNA in osteoclast differentiation rather than osteoclast survival. SIN dramatically inhibited LPS-induced TNF-α production in vitro and in vivo. Further signaling studies revealed that SIN suppressed the activation and relative gene expression of three notable nuclear factors (NF-κB, AP-1, NFAT), reduced intracellular levels of Ca2+, and down-regulated phosphorylation of MAPK p38 (but not JNK) in LPS-induced osteoclastogenesis. Focusing on upstream signals after LPS stimulation, SIN decreased expression of TLR4 and TRAF6 during osteoclast differentiation, and reduced expression of TLR4 (but not TRAF6) in osteoclast survival. These data suggest that SIN might be a potential agent for the treatment of osteolysis caused by Gram-negative bacteria infection or inflammation due to its inhibition of osteoclastogenesis through reduction of TLR4/TRAF6 expression and downstream signal transduction.
    Original languageEnglish
    Pages (from-to)66-79
    JournalEuropean Journal of Pharmacology
    Volume779
    DOIs
    Publication statusPublished - 2016

    Fingerprint

    TNF Receptor-Associated Factor 6
    Osteolysis
    Osteogenesis
    Osteoclasts
    Lipopolysaccharides
    Down-Regulation
    sinomenine
    Bone and Bones
    Transcription Factor AP-1
    p38 Mitogen-Activated Protein Kinases
    Gram-Negative Bacteria
    Matrix Metalloproteinases
    Inbred C57BL Mouse
    Alkaloids
    Skull
    Arthritis
    Signal Transduction
    Anti-Inflammatory Agents

    Cite this

    @article{58d77c2235dc490bbdd73e71eaebe250,
    title = "Sinomenine down-regulates TLR4/TRAF6 expression and attenuates lipopolysaccharide-induced osteoclastogenesis and osteolysis",
    abstract = "{\circledC} 2016 Elsevier B.V. All rights reserved. Sinomenine (SIN) is an anti-inflammatory and anti-arthritic alkaloid derived from Sinomenioum acutum. Effects of SIN on lipopolysaccharide (LPS)-induced osteolysis have not been reported. Here, we found that SIN reduced LPS-induced erosion of skull bones in C57BL/6 mice significantly. LPS can induce bone-absorbing osteoclast formation independent of RANKL in pre-osteoclastic RAW264.7 cells in vitro. Here, SIN suppressed LPS-induced osteoclast formation and osteoclast survival in RAW264.7 cells. Expression of osteoclastic-specific marker genes was also inhibited by SIN during osteoclast differentiation and osteoclast survival stimulated with LPS. SIN showed much stronger inhibitory effects on expression of Fra-1 and MMP-9 mRNA in osteoclast differentiation rather than osteoclast survival. SIN dramatically inhibited LPS-induced TNF-α production in vitro and in vivo. Further signaling studies revealed that SIN suppressed the activation and relative gene expression of three notable nuclear factors (NF-κB, AP-1, NFAT), reduced intracellular levels of Ca2+, and down-regulated phosphorylation of MAPK p38 (but not JNK) in LPS-induced osteoclastogenesis. Focusing on upstream signals after LPS stimulation, SIN decreased expression of TLR4 and TRAF6 during osteoclast differentiation, and reduced expression of TLR4 (but not TRAF6) in osteoclast survival. These data suggest that SIN might be a potential agent for the treatment of osteolysis caused by Gram-negative bacteria infection or inflammation due to its inhibition of osteoclastogenesis through reduction of TLR4/TRAF6 expression and downstream signal transduction.",
    author = "L. He and H. Duan and X. Li and S. Wang and Y. Zhang and L. Lei and Jiake Xu and S. Liu",
    year = "2016",
    doi = "10.1016/j.ejphar.2016.03.014",
    language = "English",
    volume = "779",
    pages = "66--79",
    journal = "European Journal of Pharmacology",
    issn = "0014-2999",
    publisher = "Elsevier",

    }

    Sinomenine down-regulates TLR4/TRAF6 expression and attenuates lipopolysaccharide-induced osteoclastogenesis and osteolysis. / He, L.; Duan, H.; Li, X.; Wang, S.; Zhang, Y.; Lei, L.; Xu, Jiake; Liu, S.

    In: European Journal of Pharmacology, Vol. 779, 2016, p. 66-79.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Sinomenine down-regulates TLR4/TRAF6 expression and attenuates lipopolysaccharide-induced osteoclastogenesis and osteolysis

    AU - He, L.

    AU - Duan, H.

    AU - Li, X.

    AU - Wang, S.

    AU - Zhang, Y.

    AU - Lei, L.

    AU - Xu, Jiake

    AU - Liu, S.

    PY - 2016

    Y1 - 2016

    N2 - © 2016 Elsevier B.V. All rights reserved. Sinomenine (SIN) is an anti-inflammatory and anti-arthritic alkaloid derived from Sinomenioum acutum. Effects of SIN on lipopolysaccharide (LPS)-induced osteolysis have not been reported. Here, we found that SIN reduced LPS-induced erosion of skull bones in C57BL/6 mice significantly. LPS can induce bone-absorbing osteoclast formation independent of RANKL in pre-osteoclastic RAW264.7 cells in vitro. Here, SIN suppressed LPS-induced osteoclast formation and osteoclast survival in RAW264.7 cells. Expression of osteoclastic-specific marker genes was also inhibited by SIN during osteoclast differentiation and osteoclast survival stimulated with LPS. SIN showed much stronger inhibitory effects on expression of Fra-1 and MMP-9 mRNA in osteoclast differentiation rather than osteoclast survival. SIN dramatically inhibited LPS-induced TNF-α production in vitro and in vivo. Further signaling studies revealed that SIN suppressed the activation and relative gene expression of three notable nuclear factors (NF-κB, AP-1, NFAT), reduced intracellular levels of Ca2+, and down-regulated phosphorylation of MAPK p38 (but not JNK) in LPS-induced osteoclastogenesis. Focusing on upstream signals after LPS stimulation, SIN decreased expression of TLR4 and TRAF6 during osteoclast differentiation, and reduced expression of TLR4 (but not TRAF6) in osteoclast survival. These data suggest that SIN might be a potential agent for the treatment of osteolysis caused by Gram-negative bacteria infection or inflammation due to its inhibition of osteoclastogenesis through reduction of TLR4/TRAF6 expression and downstream signal transduction.

    AB - © 2016 Elsevier B.V. All rights reserved. Sinomenine (SIN) is an anti-inflammatory and anti-arthritic alkaloid derived from Sinomenioum acutum. Effects of SIN on lipopolysaccharide (LPS)-induced osteolysis have not been reported. Here, we found that SIN reduced LPS-induced erosion of skull bones in C57BL/6 mice significantly. LPS can induce bone-absorbing osteoclast formation independent of RANKL in pre-osteoclastic RAW264.7 cells in vitro. Here, SIN suppressed LPS-induced osteoclast formation and osteoclast survival in RAW264.7 cells. Expression of osteoclastic-specific marker genes was also inhibited by SIN during osteoclast differentiation and osteoclast survival stimulated with LPS. SIN showed much stronger inhibitory effects on expression of Fra-1 and MMP-9 mRNA in osteoclast differentiation rather than osteoclast survival. SIN dramatically inhibited LPS-induced TNF-α production in vitro and in vivo. Further signaling studies revealed that SIN suppressed the activation and relative gene expression of three notable nuclear factors (NF-κB, AP-1, NFAT), reduced intracellular levels of Ca2+, and down-regulated phosphorylation of MAPK p38 (but not JNK) in LPS-induced osteoclastogenesis. Focusing on upstream signals after LPS stimulation, SIN decreased expression of TLR4 and TRAF6 during osteoclast differentiation, and reduced expression of TLR4 (but not TRAF6) in osteoclast survival. These data suggest that SIN might be a potential agent for the treatment of osteolysis caused by Gram-negative bacteria infection or inflammation due to its inhibition of osteoclastogenesis through reduction of TLR4/TRAF6 expression and downstream signal transduction.

    U2 - 10.1016/j.ejphar.2016.03.014

    DO - 10.1016/j.ejphar.2016.03.014

    M3 - Article

    VL - 779

    SP - 66

    EP - 79

    JO - European Journal of Pharmacology

    JF - European Journal of Pharmacology

    SN - 0014-2999

    ER -