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DcR3 induces cell proliferation through MAPK signaling in chondrocytes of osteoarthritis.
MedLine Citation:
PMID:  21420502     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
INTRODUCTION: : Decoy receptor 3 (DcR3), a soluble receptor belonging to the TNF receptor superfamily, competitively binds and inhibits the TNF family including Fas-ligand (Fas-L), LIGHT, and TL1A. In this study, we investigated the functions of DcR3 on osteoarthritis (OA) chondrocytes. METHODS: : Expressions of DcR3 in chondrocytes were measured by realtime RT-PCR. Expression of DcR3 in sera and joint fluids was measured by ELISA. Chondrocytes were incubated with DcR3-Fc chimera protein (DcR3-Fc) before induction of apoptosis by Fas ligand and apoptosis was detected with TUNEL staining and western blotting of caspase 8 and poly (ADP-ribose) polymerase (PARP). Chondrocytes were incubated with DcR3-Fc and the proliferation was analyzed by WST assay. Phosphorylation of ERK, P38MAPK and JNK in chondrocytes was measured by western blotting after incubation with DcR3-Fc, MEK1/2 inhibitor, or P38 MAPK inhibitor. Chondrocytes were treated with DcR3-Fc after pre-incubation with blocking antibody of Fas-L, LIGHT and TL1A, and proliferation or phosphorylation of ERK was analyzed. RESULTS: : DcR3 was expressed in OA and normal chondrocytes. DcR3-Fc protects chondrocytes from Fas-induced apoptosis. DcR3-Fc increased chondrocytes proliferation and induced the phosphorylaion of ERK specifically. DcR3-induced chondrocytes proliferation was inhibited by pre-incubation of PD098059 or blocking Fas-L antibody. DcR3 increased chondrocytes proliferation in OA chondrocytes, but did not in normal. CONCLUSION: : DcR3 regulates the proliferation of OA chondrocytes via ERK signaling and Fas-induced apoptosis. (220 words).
Authors:
Shinya Hayashi; Takayuki Nishiyama; Yasushi Miura; Takaaki Fujishiro; Noriyuki Kanzaki; Shingo Hashimoto; Tomoyuki Matsumoto; Masahiro Kurosaka; Ryosuke Kuroda
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-3-17
Journal Detail:
Title:  Osteoarthritis and cartilage / OARS, Osteoarthritis Research Society     Volume:  -     ISSN:  1522-9653     ISO Abbreviation:  -     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-3-22     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9305697     Medline TA:  Osteoarthritis Cartilage     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier Ltd.
Affiliation:
Dept. of Orthopaedic Surgery, Kobe Univ. Graduate School of Med., Kobe, Japan.
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