Animal models of arthritis in NOS2-deficient mice

Berg, Wim B. van den; Loo, Fons A. J. van de; Joosten, L.A.B.; Arntz, Onno J.

doi:10.1053/joca.1999.0228

Cited by 74 publications

(30 citation statements)

References 5 publications

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“…Two classes of enzymes, constitutive NOS (cNOS) and inducible NOS (iNOS, also called NOS2), are known; the latter is considered to be more important in pathologic conditions because it can produce much more NO than can cNOS. Studies on iNOS null mice and using iNOS inhibitors corroborated the significance of NO in progression of OA [38,39,40].…”

Section: Nitric Oxidementioning

confidence: 83%

Cell biology of osteoarthritis: The chondrocyte’s response to injury

2001

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Cartilage is comprised of a large amount of functional extracellular matrix that is made and maintained by a small number of chondrocytes, the sole resident cell type. Normal cartilage exists in a relatively steady state: that is, the anabolic processes (those that result in the synthesis of cartilage matrix components) are in equilibrium with the catabolic processes (those that result in the normal turnover of matrix molecules). If the functional extracellular matrix is disturbed by physical or molecular means, the cells respond in an attempt to repair the matrix. This stimulated activity does not result in repair due to the extent and complexity of the extracellular matrix. Eventually, the newly synthesized and activated catabolic enzymes degrade the matrix components. This review presents the cellular and molecular mechanisms that account for this activity and provides some possible solutions.

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Section: Nitric Oxidementioning

confidence: 83%

Cell biology of osteoarthritis: The chondrocyte’s response to injury

2001

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“…For example, the inhibition of IL-1 and its actions by the IL-1 receptor antagonist using gene therapy was clearly demonstrated in the rabbit OA model [58]. A role for NO was confirmed in OA models of iNOS deficient mice and the presence of iNOS specific inhibitors showed diminished joint pathology and protection against cartilage damage [59][60][61]. The potential of inhibitors which block the MAPK signaling cascade and inhibit IL-1 actions were demonstrated in animal models of rheumatoid arthritis [62] However, to date, it is not known how effective these approaches will be in the human situation [57].…”

Section: Discussionmentioning

confidence: 95%

Signal transduction pathways involving p38 MAPK, JNK, NFκB and AP-1 influences the response of chondrocytes cultured in agarose constructs to IL-1β and dynamic compression

et al. 2008

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The MAPK, AP-1 and NF-kappaB signalling pathways are involved in the upregulation of NO and PGE2 release by IL-1beta. Dynamic compression stimulates cell proliferation and proteoglycan synthesis in the presence of IL-1beta and/or inhibitors of the MAPKs and NFkappaB and AP-1 signalling pathways. This experimental approach could provide valuable information for the biophysical/pharmacological treatment of OA.

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“…They can also cause secondary synovitis, stimulate cartilage cells and synovial cells, and produce various cytokines and proteases. [37][38][39][40][41] It is also thought that pain is generated at the site of a local inflammation when cytokines induce cyclooxygenase-2 (COX-2) and produce prostaglandin E 2 . 11,42- 46 Willburger produced a fascinating report concerning the involvement of facet joint-associated inflammatory chemical factors in degenerative lumbar spinal disorders: contained in degenerated disc tissues, facet joint cartilages and subchondral bone tissues in surgical cases of human degenerative lumbar spinal disorders were multiple types of prostaglandins and leukotrienes, metabolites of arachidonic acid cascade, which were similar to the results from joint cartilages and subchondral bone tissues of osteoarthritis patients.…”

Section: Discussionmentioning

confidence: 99%