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Citations to this article

Apoptosis in rheumatoid arthritis synovium.
G S Firestein, … , M Yeo, N J Zvaifler
G S Firestein, … , M Yeo, N J Zvaifler
Published September 1, 1995
Citation Information: J Clin Invest. 1995;96(3):1631-1638. https://doi.org/10.1172/JCI118202.
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Research Article Article has an altmetric score of 9

Apoptosis in rheumatoid arthritis synovium.

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Abstract

RA synovial tissue (ST) was studied to determine if and where apoptosis occurs in situ. Genomic DNA was extracted from 5 RA and 1 osteoarthritis ST samples. Agarose gel electrophoresis demonstrated DNA ladders characteristic for apoptosis from each tissue. In situ and labeling (ISEL) was used to identify DNA strand breaks consistent with apoptosis in frozen sections. 12 RA and 4 osteoarthritis ST were studied by ISEL and all were positive, but only 2 of 4 normal tissues were positive. The primary location of apopotic cells was the synovial lining. Some sublining cells were also positive, but lymphoid aggregate staining was conspicuously absent. Immunohistochemistry and ISEL were combined and showed that the lining cells with DNA strand breaks were mainly macrophages, although some fibroblastlike cells were also labeled. Sublining cells with fragmented DNA included macrophages and fibroblasts, but T cells in lymphoid aggregates, which expressed large amounts of bcl-2, were spared. DNA strand breaks in cultured fibroblastlike synoviocytes was assessed using ISEL. Apoptosis could be induced by actinomycin D, anti-fas antibody, IL-1, and TNF-alpha but not by IFN-gamma. Fas expression was also detected on fibroblast-like synoviocytes using flow cytometry. Therefore, DNA strand breaks occur in synovium of patients with arthritis. Cytokines regulate this process, and the cytokine profile in RA (high IL-1/TNF; low IFN-gamma) along with local oxidant injury might favor induction of apoptosis.

Authors

G S Firestein, M Yeo, N J Zvaifler

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Citations to this article in year 2010 (12)

Title and authors Publication Year
Fibroblast-like synoviocytes: key effector cells in rheumatoid arthritis
B Bartok, GS Firestein
Immunological Reviews 2010
Current concepts in the genetic diagnostics of rheumatoid arthritis
ZB Nagy, M Csanád, K Tóth, B Börzsönyi, C Demendi, J Rigó, JG Joó
Expert Review of Molecular Diagnostics 2010
Cilostazol enhances apoptosis of synovial cells from rheumatoid arthritis patients with inhibition of cytokine formation via Nrf2-linked heme oxygenase 1 induction
SY Park, SW Lee, HK Shin, WT Chung, WS Lee, BY Rhim, KW Hong, CD Kim
Arthritis & Rheumatism 2010
Liposome-bound APO2L/TRAIL is an effective treatment in a rabbit model of rheumatoid arthritis
L Martinez-Lostao, F Garcí´a-Alvarez, G Basáñez, E Alegre-Aguarón, P Desportes, L Larrad, J Naval, MJ Martí´nez-Lorenzo, A Anel
Arthritis & Rheumatism 2010
Therapeutic effects of astragalus polysaccharides on inflammation and synovial apoptosis in rats with adjuvant-induced arthritis
JB JIANG, JD QIU, LH YANG, JP HE, GW SMITH, HQ LI
International Journal of Rheumatic Diseases 2010
Extracellular calreticulin is present in the joints of patients with rheumatoid arthritis and inhibits FasL (CD95L)-mediated apoptosis of T cells
JM Tarr, PG Winyard, B Ryan, LW Harries, R Haigh, N Viner, P Eggleton
Arthritis & Rheumatism 2010
Small molecules regulating apoptosis in the synovium in rheumatoid arthritis
AI Dubikov, SG Kalinichenko
Scandinavian Journal of Rheumatology 2010
Aberrant Reactive Oxygen and Nitrogen Species Generation in Rheumatoid Arthritis (RA): Causes and Consequences for Immune Function, Cell Survival, and Therapeutic Intervention
DC Phillips, HK Dias, GD Kitas, HR Griffiths
Antioxidants & Redox Signaling 2010
Slug suppression induces apoptosis via Puma transactivation in rheumatoid arthritis fibroblast-like synoviocytes treated with hydrogen peroxide
HS Cha, EK Bae, JK Ahn, J Lee, KS Ahn, EM Koh
Experimental & molecular medicine 2010
Expression of FLICE-inhibitory Protein in Synovial Tissue and Its Association with Synovial Inflammation in Juvenile Idiopathic Arthritis
F Wu, L Wu, X Luo, M Yang, Z Tang, C Xie, J Zhou, J Guan, G Yuan
Chinese Medical Sciences Journal 2010
Paclitaxel Induced Caspase-Independent Mitotic Catastrophe in Rabbit Articular Chondrocyte
JH Im, SJ Kim
Journal of Life Science 2010
Attenuation of oxidative stress and alteration of hepatic tissue ultrastructure by D-pinitol in streptozotocin-induced diabetic rats
S Sivakumar, P Palsamy, SP Subramanian
Free Radical Research 2010

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