Apoptosis induced by nitric oxide is associated with nuclear p53 protein expression in cultured osteoarthritic synoviocytes

Borderie, Didier; Hilliquin, P.; Hernvann, Alain; Lemaréchal, Hervé; Menkès, C J; Ekindjian, Ohvanesse G.

doi:10.1053/joca.1998.0209

Cited by 27 publications

(21 citation statements)

References 27 publications

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“…In fact, an increase of NO, tumour necrosis factor , interleukin 1, metalloproteases (MMP) and reactive oxygen radicals (ROS) is observed in OA, demonstrating the participation of these factors to the genesis and maintainance of degenerative processes in OA (Osborn et al, 1989;Moskowitz, 1993;Lotz et al, 1995;Blanco et al, 2000). NO is mainly produced by chondrocyte, induces apoptosis of the chondrocyte itself (Attisano et al, 1994;Borderie et al, 1999;Fukui et al, 2001;Purple et al, 2001), and inhibits the synthesis of components of cartilage matrix such as collagen type II and GAGs; NO, moreover, increases the activity of MMP, decreases the proliferative response to the Insulin-like Growth Factor-1 (IGF-1) and reduces the endogenous production of Transforming Growth Factor (TGF ), by chondrocyte, furtherly decreasing the synthesis of GAGs and of collagen fibers. Recent in vitro studies (Blanco et al, 2000) have demonstrated that CS blocks the synthesis of NO at the articular level.…”

Section: Discussionmentioning

confidence: 99%

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice

Caraglia¹,

Beninati²,

Giuberti³

et al. 2005

Exp Mol Med

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The administration of mineral sulphur water is an alternative experimental approach for the treatment of rheumatic diseases, such as osteoarthritis (OA), that cause the degeneration of bone and cartilage and sufferance to the patients. Chondroitin sulfate (CS) is a symptomatic slow acting nutropeucital agent currently used in molecular therapy of OA. Therefore, we have studied the role and efficacy of the selective soil paste from the mineral sulphur enriched spring (mud)-therapy alone or in combination with CS in the treatment of OA. The study was performed on 40 C57 Black 6N mice, an experimental model which spontaneously develop an osteoarthritic process. The animals were divided in 4 groups and were treated with the single agents or with the combination. After 30 days of treatment all the mice were sacrificed and right knees and blood were collected. It was found that CS determined a reduction of radiological and histological features of chondrodegeneration and that mud-therapy increased the effects of CS in the animal group treated with the combination. However, the effects of thermal therapy alone were not statistically significant. Since OA is characterized by an increase of the production of nitric oxide (NO) by chondrocytes in extracellular matrix with its consequent elevation in serum and synovial fluid, we have evaluated the effects of the treatments on serum NO levels. CS alone induced a statistically significant reduction of NO serum levels (90 ± 13 µM vs 219 ± 60 µM of control group, P 0.05) while mud-therapy alone induced a not statistically significant reduction of serum NO (170 ± 62 µM, P 0.05). However, the latter strongly potentiated the decrease of serum NO induced by CS (31 ± 1.5 µM) with a high statistical significance if compared to both the control group (P 0.01) and the CS-treated group (P 0.05). In conclusion, this study demonstrates that mud-therapy with sulphur mineral water could represent an important phase of the therapeutic strategy of OA. This experimental strategy could integrate and potentiate the standard pharmacological tools. Moreover, we have set a valid experimental in vivo model for the study of the thermal effects on the development of OA.

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Section: Discussionmentioning

confidence: 99%

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice

Caraglia¹,

Beninati²,

Giuberti³

et al. 2005

Exp Mol Med

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“…44 Furthermore, the appearance of p53 and iNOS in apoptotic macrophages is established in human atherosclerotic lesions. 66 Moreover, a positive correlation between NO formation and apoptosis is also implied for articular cartilage samples from humans with osteoarthritis 67,68 or for the occurrence of human lupus nephritis. 69 Generally, it appears that NO is endowed with the capability to initiate apoptosis in cellular systems, co-cultures, and in vivo.…”

Section: Lessons From Disease Statesmentioning

confidence: 99%

Nitric oxide (NO): an effector of apoptosis

1999

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It is appreciated that the production of nitric oxide (NO) from Larginine metabolism is an essential determinate of the innate immune system, important for nonspecific host defense, as well as tumor and pathogen killing. Cytotoxicity as a result of a substantial NO-formation is established to initiate apoptosis, characterized by upregulation of the tumor suppressor p53, changes in the expression of pro-and anti-apoptotic Bcl-2 family members, cytochrome c relocation, activation of caspases, chromatin condensation, and DNA fragmentation. Proof for the involvement of NO was demonstrated by blocking adverse effects by NO-synthase inhibition. However, NOtoxicity is not a constant value and NO may achieve cell protection as well. In part this is understood by transcription and translation of protective proteins, such as cyclooxygenase-2. Alternatively, protection may result as a consequence of a diffusion controlled NO/O 2 7 (superoxide) interaction that redirects the apoptotic initiating activity of NO towards protection. NO is endowed with the unique ability to initiate and to block apoptosis, depending on multiple variables that exist to be elucidated. The crosstalk between cell destructive and protective signaling pathways under the modulatory influence of NO will determine the impact of NO in apoptotic cell death and survival.

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“…6A). NO was chosen as a pro-apoptotic agent owing to its overproduction in the RA joint and its ability to induce apoptosis of FLSs in vitro (21,22). Whereas the protective effect of S1P on SNP-mediated FLS apoptosis was not blocked by a pretreatment of the cells with the S1P 2 antagonist JTE-013 and the S1P 3 antagonist CAY10444 (data not shown), the S1P 1 agonist SEW2871 significantly reduced SNP-mediated FLS cell apoptosis in a concentration-dependent manner (Fig.…”

Section: Protective Effect Of S1p On Snp-mediated Fls Apoptosismentioning

confidence: 99%

Specific and overlapping sphingosine-1-phosphate receptor functions in human synoviocytes: impact of TNF-α

Chang

Fernandes

Turgeon

et al. 2008

Journal of Lipid Research

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Sphingosine-1-phosphate (S1P), via interaction with its G protein-coupled receptors, regulates various physiological and pathological responses. The present study investigated the role of S1P/S1P receptor signaling in several functional responses of human fibroblast-like synoviocytes (FLSs) that may contribute to the pathogenesis of rheumatoid arthritis (RA). We report that FLSs express the S1P 1 , S1P 2 , and S1P 3 receptors. Moreover, exogenously applied S1P induces FLS 1) migration, 2) secretion of inflammatory cytokines/chemokines, and 3) protection from apoptosis. Using specific S1P receptor agonists/antagonists, we determined that S1P stimulates FLS migration through S1P 1 and S1P 3 , induces cytokine/chemokine secretion through S1P 2 and S1P 3 , and protects from cell apoptosis via S1P 1 . The S1P-mediated cell motility and cytokine/chemokine secretion seem to be regulated by the p38 mitogen-activated protein kinase (MAPK), p42/44 MAPK, and Rho kinase signal transduction pathways. Interestingly, treatment of FLSs with tumor necrosis factor-a increases S1P 3 expression and correlates with the enhancement of S1P-induced cytokine/ chemokine production. Our data suggest that S1P 1 , S1P 2 , and S1P 3 play essential roles in the pathogenesis of RA by modulating FLS migration, cytokine/chemokine production, and cell survival. Moreover, the cytokine-rich environment of the inflamed synovium may synergize with S1P signaling to exacerbate the clinical manifestations of this autoimmune disease.-Zhao, C., M. J. Fernandes, M. Turgeon, S. Tancrède, J. Di Battista, P. E. Poubelle, and S. G. Bourgoin.

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Apoptosis induced by nitric oxide is associated with nuclear p53 protein expression in cultured osteoarthritic synoviocytes

Abstract: This study demonstrates the potential role of NO for the induction of synoviocyte apoptosis in OA. The increased expression of p53 in the nucleus may play a protective role in the control of apoptosis.

Cited by 27 publications

References 27 publications

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice

Alternative therapy of earth elements increases the chondroprotective effects of chondroitin sulfate in mice

Nitric oxide (NO): an effector of apoptosis

Specific and overlapping sphingosine-1-phosphate receptor functions in human synoviocytes: impact of TNF-α

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