RGD Reference Report - Anti-DR5 mAb ameliorate adjuvant arthritis rats through inducing synovial cells apoptosis. - Rat Genome Database

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Anti-DR5 mAb ameliorate adjuvant arthritis rats through inducing synovial cells apoptosis.

Authors: Li, W  Liu, Z  Zhuang, G  Yin, P  Tao, H  Qiu, J  Hu, Q  Zhang, J 
Citation: Li W, etal., Exp Biol Med (Maywood). 2009 Dec;234(12):1468-76.
RGD ID: 4142856
Pubmed: PMID:19934367   (View Abstract at PubMed)
DOI: DOI:10.3181/0811-RM-342   (Journal Full-text)

OBJECTIVE: Study the therapeutic effects and immunoregulatory mechanisms of anti-DR5 mAb on adjuvant arthritis (AA) rats. METHODS: AA rats induced by CFA, were treated with anti-DR5 mAb through mainline administration. Effect on the synovial membranes of the tissues was detected by H&E staining. Flow cytometry and MTT assay were used for detecting the induced apoptosis in an in vitro system and TUNEL assay was used for analysis in an in vivo system. The involvement of the apoptotic pathway was further proved by a caspase inhibition assay. RESULTS: Anti-DR5 mAb could induce synovial cell apoptosis in an in vitro system, which was related with the mRNA expression of DR5 on the cell surface. The mRNA expressions of c-myc and bcl-2 were decreased in synovial cells and those of p21, p53, and bax were increased. The protein expressions of caspase-8/3/9, RANKL, JNK2, and c-Jun were raised and that of bcl-2 was decreased. When the caspase inhibitor was added to the synovial cells treated with anti-DR5 mAb, it showed a dose-dependence inhibition effect, indicating that anti-DR5 mAb inducing apoptosis might be through the caspase pathway. CONCLUSION: This study shows that anti-DR5 mAb can ameliorate arthritic symptoms. The mechanisms of the treatment are related to the increase in synovial cell apoptosis by regulating the mRNA expression of DR5 and apoptosis-related genes, prolonging the duration of the cell cycle by modulation of the mRNA expression of cell cycle-related genes, and the protein expression of the molecules in the caspase pathway and RANKL, JNK2, and c-Jun.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Tnfrsf10bRatextrinsic apoptotic signaling pathway via death domain receptors  IMP  RGD 

Molecular Pathway Annotations    Click to see Annotation Detail View

RGD Manual Annotations


  
Objects Annotated

Genes (Rattus norvegicus)
Tnfrsf10b  (TNF receptor superfamily member 10b)

Genes (Mus musculus)
Tnfrsf10b  (tumor necrosis factor receptor superfamily, member 10b)

Genes (Homo sapiens)
TNFRSF10B  (TNF receptor superfamily member 10b)


Additional Information