RGD Reference Report - Sinomenine suppresses osteoclast formation and Mycobacterium tuberculosis H37Ra-induced bone loss by modulating RANKL signaling pathways. - Rat Genome Database

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Sinomenine suppresses osteoclast formation and Mycobacterium tuberculosis H37Ra-induced bone loss by modulating RANKL signaling pathways.

Authors: Li, Xiaojuan  He, Longgang  Hu, Yiping  Duan, Heng  Li, Xianglian  Tan, Suiyi  Zou, Min  Gu, Chunping  Zeng, Xiangzhou  Yu, Le  Xu, Jiake  Liu, Shuwen 
Citation: Li X, etal., PLoS One. 2013 Sep 16;8(9):e74274. doi: 10.1371/journal.pone.0074274. eCollection 2013.
RGD ID: 42721982
Pubmed: PMID:24066131   (View Abstract at PubMed)
PMCID: PMC3774760   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0074274   (Journal Full-text)

Receptor activator of NF-κB ligand (RANKL) is essential for osteoclastogenesis. Targeting RANKL signaling pathways has been an encouraging strategy for treating lytic bone diseases such as osteoporosis and rheumatoid arthritis (RA). Sinomenine (SIN), derived from Chinese medicinal plant Sinomenioumacutum, is an active compound to treat RA, but its effect on osteoclasts has been hitherto unknown. In the present study, SIN was found to ameliorate M. tuberculosis H37Ra (Mt)-induced bone loss in rats with a decreased serum level of TRACP5b and RANKL, and an increased level of osteoprotegerin (OPG). In vitro study also showed that SIN could inhibit RANKL-induced osteoclast formation and bone resorption. The osteoclastic specific marker genes induced by RANKL including c-Src, MMP-9, TRACP were inhibited by SIN in a dose dependent manner. Signal transduction studies showed that SIN could obviously reduce the expression of RANK adaptor molecule TRAF6 and down-regulate RANKL-induced NF-κB activation. It decreased the RANKL-induced p38, JNK posphorylation but not ERK1/2 posphorylation. SIN could also reduce RANKL-mediated calcium influx which is associated with TRAF6/c-Src complex. Finally, SIN suppressed RANKL induced AP-1 and NFAT transcription, as well as the gene expression of NFATc1 and AP-1 components (Fra-1, Fra-2, c-Fos). The protein expression of c-Fos and TRAF6 were also inhibited by SIN after RANKL stimulation. Taken together, SIN could attenuate osteoclast formation and Mt-induced bone loss by mediating RANKL signaling pathways.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TNFRSF11BHumanExperimental Arthritis treatmentISOTnfrsf11b (Rattus norvegicus)Sinomenine CHEBI:9163RGD 
Tnfrsf11bMouseExperimental Arthritis treatmentISOTnfrsf11b (Rattus norvegicus)Sinomenine CHEBI:9163RGD 
Tnfrsf11bRatExperimental Arthritis treatmentIEP Sinomenine CHEBI:9163RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tnfrsf11b  (TNF receptor superfamily member 11B)

Genes (Mus musculus)
Tnfrsf11b  (tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin))

Genes (Homo sapiens)
TNFRSF11B  (TNF receptor superfamily member 11b)


Additional Information