Nitric oxide in osteoarthritis

Abstract

Activated articular chondrocytes produce large amounts of nitric oxide (NO), and there is increasing evidence that this is involved in the etiopathogenesis of osteoarthritis (OA). Because of its short half-life, the biological effects of endogenously produced NO are likely to occur locally within the cartilage. We have observed that inhibitors of NO synthases relieve the inhibition of matrix synthesis that otherwise occurs in response to IL-1. To avoid the use of inhibitors, we have recently transduced chondrocytes with the iNOS (NOS-2) gene and confirmed the ability of the endogenously produced NO to inhibit matrix synthesis. Despite the high levels of NO made by these cells, there was no evidence of apoptosis or other forms of cell death. NO was also shown to inhibit the production of TGF-beta(1)by cells treated with IL-1, as well as to decrease matrix production in response to IGF-1. The hypothesis that NO inhibits matrix production by interfering with important autocrine and paracrine factors should be entertained.

Tumor necrosis factor α activation of the apoptotic cascade in murine articular chondrocytes is associated with the induction of metalloproteinases and specific pro‐resorptive factors

“…However, numerous studies have shown that OPG levels will rise in a coordinated manner when RANKL levels are increasing. This is consistent with the observation of elevated OPG in synovial fluid from RA patients but not from OA patients (36). In relation to this finding, we observed an opposite effect of TNF␣ on OPG expression in repair chondrocytes isolated from fracture calluses, suggesting that while some actions of TNF␣ appear to be the same for all chondrocytes, other activities may vary between growth and articular chondrocytes.…”

Interleukin-1 Induces Pro-Mineralizing Activity of Cartilage Tissue Transglutaminase and Factor XIIIa

“…43 We observed that the NO donor Noc-12 (2.5 to 25 mol/L), and the peroxynitrite generator Sin-1 (1 to 10 mol/L) 44 shared the ability of IL-1 to induce TGase activity in cultured normal knee meniscal cells, although Noc-12 and Sin-1 were less effective than IL-1 at inducing TGase activity (Figure 7). Tumor necrosis factor (TNF)-␣, which also acts on chondrocytes, 45,46 stimulated increased TGase activity in cultured normal knee meniscal cells (Figure 7).…”

Cartilage tissue engineering for degenerative joint disease☆

“…Finally, IL-1 and TNF-α increase nitric oxide synthase leading to an increase of NO [60]. NO radicals have deleterious effect in joint cartilage including downregulation of matrix synthesis and upregulation matrix degradation via activation of MMPs [61][62][63]. Furthermore, NO increases chondrocyte susceptibility to oxidants while free radicals produced by NO were also shown to induce chondrocyte apoptosis [44,64,65].…”