Nitric oxide is a mediator of apoptosis in the rheumatoid joint

R J van't Hof, L Hocking, P K Wright, S H Ralston

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Objective. To study the role of nitric oxide (NO) derived from the inducible nitric oxide synthase (iNOS) pathway in the induction of apoptosis in the rheumatoid joint.

Methods. Joint tissue was obtained from four rheumatoid arthritis (RA) patients, three osteoarthritis patients and two patients with a fractured neck of the femur (NOF#), and apoptotic cells were identified in cryosections using the TUNEL (terminal dUTP nick end labelling) assay. Expression of iNOS was determined using immunohistochemistry. NO synthesis and the effect of NOS inhibitors on apoptosis levels were studied in explant cultures of RA cartilage and synovium.

Results. Numbers of apoptotic cells were greatly increased in rheumatoid synovium and articular cartilage compared with NOF# and osteoarthritic synovium. Immunohistochemistry showed co-localization of iNOS staining and apoptosis in the synovial lining layer and articular cartilage. The NOS inhibitor L-NMMA (L-N-G-monomethylarginine) strongly inhibited apoptosis in explant cultures of synovium and cartilage, and this was reversed by the NO donor S-nitroso-acetyl-penicillamine.

Conclusion. This study indicates that NO acts as a mediator of apoptosis in RA and suggests that NOS inhibitors reverse this process.

Original languageEnglish
Pages (from-to)1004-1008
Number of pages5
JournalRheumatology
Volume39
Issue number9
DOIs
Publication statusPublished - 2000

Keywords

  • rheumatoid arthritis
  • cytokines
  • nitric oxide
  • apoptosis
  • cartilage
  • synovium
  • djuvant arthritis
  • FAS antigen
  • synthase
  • cells
  • synoviocytes
  • chondrocytes
  • suppression

Cite this

van't Hof, R. J., Hocking, L., Wright, P. K., & Ralston, S. H. (2000). Nitric oxide is a mediator of apoptosis in the rheumatoid joint. Rheumatology, 39(9), 1004-1008. https://doi.org/10.1093/rheumatology/39.9.1004

Nitric oxide is a mediator of apoptosis in the rheumatoid joint. / van't Hof, R J ; Hocking, L ; Wright, P K ; Ralston, S H .

In: Rheumatology, Vol. 39, No. 9, 2000, p. 1004-1008.

Research output: Contribution to journalArticle

van't Hof, RJ, Hocking, L, Wright, PK & Ralston, SH 2000, 'Nitric oxide is a mediator of apoptosis in the rheumatoid joint', Rheumatology, vol. 39, no. 9, pp. 1004-1008. https://doi.org/10.1093/rheumatology/39.9.1004
van't Hof, R J ; Hocking, L ; Wright, P K ; Ralston, S H . / Nitric oxide is a mediator of apoptosis in the rheumatoid joint. In: Rheumatology. 2000 ; Vol. 39, No. 9. pp. 1004-1008.
@article{cac6de5df6d246b98d703613603bbcfe,
title = "Nitric oxide is a mediator of apoptosis in the rheumatoid joint",
abstract = "Objective. To study the role of nitric oxide (NO) derived from the inducible nitric oxide synthase (iNOS) pathway in the induction of apoptosis in the rheumatoid joint.Methods. Joint tissue was obtained from four rheumatoid arthritis (RA) patients, three osteoarthritis patients and two patients with a fractured neck of the femur (NOF#), and apoptotic cells were identified in cryosections using the TUNEL (terminal dUTP nick end labelling) assay. Expression of iNOS was determined using immunohistochemistry. NO synthesis and the effect of NOS inhibitors on apoptosis levels were studied in explant cultures of RA cartilage and synovium.Results. Numbers of apoptotic cells were greatly increased in rheumatoid synovium and articular cartilage compared with NOF# and osteoarthritic synovium. Immunohistochemistry showed co-localization of iNOS staining and apoptosis in the synovial lining layer and articular cartilage. The NOS inhibitor L-NMMA (L-N-G-monomethylarginine) strongly inhibited apoptosis in explant cultures of synovium and cartilage, and this was reversed by the NO donor S-nitroso-acetyl-penicillamine.Conclusion. This study indicates that NO acts as a mediator of apoptosis in RA and suggests that NOS inhibitors reverse this process.",
keywords = "rheumatoid arthritis, cytokines, nitric oxide, apoptosis, cartilage, synovium, djuvant arthritis, FAS antigen, synthase, cells, synoviocytes, chondrocytes, suppression",
author = "{van't Hof}, {R J} and L Hocking and Wright, {P K} and Ralston, {S H}",
year = "2000",
doi = "10.1093/rheumatology/39.9.1004",
language = "English",
volume = "39",
pages = "1004--1008",
journal = "Rheumatology",
issn = "1462-0324",
publisher = "OXFORD UNIV PRESS INC",
number = "9",

}

TY - JOUR

T1 - Nitric oxide is a mediator of apoptosis in the rheumatoid joint

AU - van't Hof, R J

AU - Hocking, L

AU - Wright, P K

AU - Ralston, S H

PY - 2000

Y1 - 2000

N2 - Objective. To study the role of nitric oxide (NO) derived from the inducible nitric oxide synthase (iNOS) pathway in the induction of apoptosis in the rheumatoid joint.Methods. Joint tissue was obtained from four rheumatoid arthritis (RA) patients, three osteoarthritis patients and two patients with a fractured neck of the femur (NOF#), and apoptotic cells were identified in cryosections using the TUNEL (terminal dUTP nick end labelling) assay. Expression of iNOS was determined using immunohistochemistry. NO synthesis and the effect of NOS inhibitors on apoptosis levels were studied in explant cultures of RA cartilage and synovium.Results. Numbers of apoptotic cells were greatly increased in rheumatoid synovium and articular cartilage compared with NOF# and osteoarthritic synovium. Immunohistochemistry showed co-localization of iNOS staining and apoptosis in the synovial lining layer and articular cartilage. The NOS inhibitor L-NMMA (L-N-G-monomethylarginine) strongly inhibited apoptosis in explant cultures of synovium and cartilage, and this was reversed by the NO donor S-nitroso-acetyl-penicillamine.Conclusion. This study indicates that NO acts as a mediator of apoptosis in RA and suggests that NOS inhibitors reverse this process.

AB - Objective. To study the role of nitric oxide (NO) derived from the inducible nitric oxide synthase (iNOS) pathway in the induction of apoptosis in the rheumatoid joint.Methods. Joint tissue was obtained from four rheumatoid arthritis (RA) patients, three osteoarthritis patients and two patients with a fractured neck of the femur (NOF#), and apoptotic cells were identified in cryosections using the TUNEL (terminal dUTP nick end labelling) assay. Expression of iNOS was determined using immunohistochemistry. NO synthesis and the effect of NOS inhibitors on apoptosis levels were studied in explant cultures of RA cartilage and synovium.Results. Numbers of apoptotic cells were greatly increased in rheumatoid synovium and articular cartilage compared with NOF# and osteoarthritic synovium. Immunohistochemistry showed co-localization of iNOS staining and apoptosis in the synovial lining layer and articular cartilage. The NOS inhibitor L-NMMA (L-N-G-monomethylarginine) strongly inhibited apoptosis in explant cultures of synovium and cartilage, and this was reversed by the NO donor S-nitroso-acetyl-penicillamine.Conclusion. This study indicates that NO acts as a mediator of apoptosis in RA and suggests that NOS inhibitors reverse this process.

KW - rheumatoid arthritis

KW - cytokines

KW - nitric oxide

KW - apoptosis

KW - cartilage

KW - synovium

KW - djuvant arthritis

KW - FAS antigen

KW - synthase

KW - cells

KW - synoviocytes

KW - chondrocytes

KW - suppression

U2 - 10.1093/rheumatology/39.9.1004

DO - 10.1093/rheumatology/39.9.1004

M3 - Article

VL - 39

SP - 1004

EP - 1008

JO - Rheumatology

JF - Rheumatology

SN - 1462-0324

IS - 9

ER -