Tao Cheng1, Jian Wu2, Yaozeng Xu3, Cuiping Liu2, Huayong Zhang4, Mingjun Wang5. 1. Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China. chengtao0526@126.com. 2. Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China. 3. Department of Orthopedics, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China. 4. Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing, 210008, China. 5. Department of Rheumatology, The First Affiliated Hospital of Soochow University, Suzhou, 215000, China. dlwmj@sina.com.
Abstract
INTRODUCTION: A genome-wide association analysis revealed a rheumatoid arthritis (RA)-risk-associated genetic locus on chromosome 9, which contained the tumor necrosis factor receptor-associated factor 1 (TRAF1). However, the detail mechanism by TRAF1 signaled to fibroblast-like synoviocytes (FLSs) apoptosis remains to be fully understood. MATERIALS AND METHODS: Synovial tissue of 10 RA patients and osteoarthritis patients were obtained during joint replacement surgery. We investigated TRAF1 level and FLSs apoptosis percentage in vivo and elucidated the mechanism involved in the regulation of apoptotic process in vitro. RESULTS: We proved the significant increase of TRAF1 level in FLSs of RA patients and demonstrated that TRAF1 level correlated positively with DAS28 score and negatively with FLSs apoptosis. Treatment with siTRAF1 was able to decrease MMPs levels and the phosphorylated forms of JNK/NF-κB in vitro. Moreover, JNK inhibitor could attenuate expression of MMPs and increase percentage of apoptosis in RA-FLSs, while siTRAF1 could not promote apoptosis when RA-FLSs were pretreated with JNK activator. CONCLUSIONS: High levels of TRAF1 in RA synovium play an important role in the synovial hyperplasia of RA by suppressing apoptosis through activating JNK/NF-kB-dependent signaling pathways in response to the engagement of CD40.
INTRODUCTION: A genome-wide association analysis revealed a rheumatoid arthritis (RA)-risk-associated genetic locus on chromosome 9, which contained the tumor necrosis factor receptor-associated factor 1 (TRAF1). However, the detail mechanism by TRAF1 signaled to fibroblast-like synoviocytes (FLSs) apoptosis remains to be fully understood. MATERIALS AND METHODS: Synovial tissue of 10 RA patients and osteoarthritis patients were obtained during joint replacement surgery. We investigated TRAF1 level and FLSs apoptosis percentage in vivo and elucidated the mechanism involved in the regulation of apoptotic process in vitro. RESULTS: We proved the significant increase of TRAF1 level in FLSs of RA patients and demonstrated that TRAF1 level correlated positively with DAS28 score and negatively with FLSs apoptosis. Treatment with siTRAF1 was able to decrease MMPs levels and the phosphorylated forms of JNK/NF-κB in vitro. Moreover, JNK inhibitor could attenuate expression of MMPs and increase percentage of apoptosis in RA-FLSs, while siTRAF1 could not promote apoptosis when RA-FLSs were pretreated with JNK activator. CONCLUSIONS: High levels of TRAF1 in RA synovium play an important role in the synovial hyperplasia of RA by suppressing apoptosis through activating JNK/NF-kB-dependent signaling pathways in response to the engagement of CD40.
Authors: Lucía Cabal-Hierro; Montserrat Rodríguez; Noelia Artime; Julián Iglesias; Lorea Ugarte; Miguel A Prado; Pedro S Lazo Journal: Cell Signal Date: 2014-08-22 Impact factor: 4.315
Authors: Robert M Plenge; Mark Seielstad; Leonid Padyukov; Annette T Lee; Elaine F Remmers; Bo Ding; Anthony Liew; Houman Khalili; Alamelu Chandrasekaran; Leela R L Davies; Wentian Li; Adrian K S Tan; Carine Bonnard; Rick T H Ong; Anbupalam Thalamuthu; Sven Pettersson; Chunyu Liu; Chao Tian; Wei V Chen; John P Carulli; Evan M Beckman; David Altshuler; Lars Alfredsson; Lindsey A Criswell; Christopher I Amos; Michael F Seldin; Daniel L Kastner; Lars Klareskog; Peter K Gregersen Journal: N Engl J Med Date: 2007-09-05 Impact factor: 91.245
Authors: Hannah Greenfeld; Kaoru Takasaki; Michael J Walsh; Ina Ersing; Katharina Bernhardt; Yijie Ma; Bishi Fu; Camille W Ashbaugh; Jackson Cabo; Sarah B Mollo; Hufeng Zhou; Shitao Li; Benjamin E Gewurz Journal: PLoS Pathog Date: 2015-05-21 Impact factor: 6.823