Endothelin-1 in monolayer cultures of articular chondrocytes from young and old rats: regulation by growth factors and cytokines

Messai, Habib; Khatib, Abdel‐Majid; Lebrun, Gaëlle; Aubin, Philippe; Moldovan, Florina; Fiet, J.; Mitrović, D

doi:10.1016/s0047-6374(99)00117-7

Cited by 13 publications

(12 citation statements)

References 34 publications

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“…Many studies have proven that EDN1 is highly expressed and demonstrates very important functions in the ovary and granulosa cells . FSH, hCG, IGF1, and GnRH regulate EDN1 expression in the ovary . We found that EDN1 could be upregulated by melatonin in pig GCs.…”

Section: Discussionmentioning

confidence: 63%

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Liu

Yang

et al. 2019

Journal of Pineal Research

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The interaction of granulosa cells (GCs) with oocytes is important to regulate follicle development. The exogenous melatonin promoting the maturation of oocytes by GCs has been approved in pig, however, the transcriptome profile and the functions of the genes regulated by melatonin in GCs have not yet to be fully characterized. In this study, we found melatonin could stimulate the synthesis of estradiol in pig GCs. The RNA‐seq was used to explore the effects of melatonin on gene expression, a total of 89 differentially expressed genes (DEGs) were identified. Gene ontology analysis showed DEGs which associated with regulation of cell proliferation, cell cycle, and anti‐apoptosis were significantly enriched. The functions of two DEGs, NOTCH2 and FILIP1L, were studied in pig GCs. The results showed that NOTCH2 inhibited the synthesis of estradiol, but FILIP1L promoted the synthesis of estradiol. Furthermore, inhibiting NOTCH2 in granulosa cells cocultured with cumulus‐oocyte‐complexes had no obvious effect on the maturation of pig oocyte, but could upregulate the cleavage rate of oocyte. We proved that FILIP1L had no effect on the maturation and cleavage of pig oocytes. Our work deepens the understanding of melatonin's effects on GCs and oocyte. The DEGs we found will be beneficial to reveal mechanisms of melatonin acting on GCs and oocytes and design the pharmacological interventions.

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Section: Discussionmentioning

confidence: 63%

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Liu

Yang

et al. 2019

Journal of Pineal Research

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“…Interestingly, using a specific immunoassay measuring the C telopeptide of type II collagen fragments on OA cartilage explants, we also found that the level of the cleaved collagen fragments were significantly increased in the presence of both IL-1β and ET-1 with a more potent effect observed for ET-1. This could be explained by a putative synergy between ET-1 and IL-1β as ET-1 induces IL-1β and as IL-1β has a positive feedback on ET-1 synthesis [19,27]. …”

Section: Discussionmentioning

confidence: 99%

Untitled

et al. 2005

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The mechanism of endothelin-1 (ET-1)-induced nitric oxide (NO) production, MMP-1 production and MMP-13 production was investigated in human osteoarthritis chondrocytes. The cells were isolated from human articular cartilage obtained at surgery and were cultured in the absence or presence of ET-1 with or without inhibitors of protein kinase or LY83583 (an inhibitor of soluble guanylate cyclase and of cGMP). MMP-1, MMP-13 and NO levels were then measured by ELISA and Griess reaction, respectively. Additionally, inducible nitric oxide synthase (iNOS) and phosphorylated forms of p38 mitogen-activated protein kinase, p44/42, stress-activated protein kinase/Jun-N-terminal kinase and serine-threonine Akt kinase were determined by western blot. Results show that ET-1 greatly increased MMP-1 and MMP-13 production, iNOS expression and NO release. LY83583 decreased the production of both metalloproteases below basal levels, whereas the inhibitor of p38 kinase, SB202190, suppressed ET-1-stimulated production only. Similarly, the ET-1-induced NO production was partially suppressed by the p38 kinase inhibitor and was completely suppressed by the protein kinase A kinase inhibitor KT5720 and by LY83583, suggesting the involvement of these enzymes in relevant ET-1 signalling pathways. In human osteoarthritis chondrocytes, ET-1 controls the production of MMP-1 and MMP-13. ET-1 also induces NO release via iNOS induction. ET-1 and NO should thus become important target molecules for future therapies aimed at stopping cartilage destruction.

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“…However, as was previously shown by Khatib et al (39), ET‐1 down‐regulated proteoglycan biosynthesis in aging animal chondrocytes. Because significant architectural changes have been observed in the structure of proteoglycans as a result of aging, and because ET‐1 and ET‐1 receptors have been shown to be up‐regulated in chondrocytes from aging animals (25, 40), characterization of these effects would be an interesting area of future investigation. It is also known that proteoglycans are progressively depleted and that chondrocytes appear to be unable to fully compensate for this depletion, resulting in a net loss of matrix.…”

Section: Discussionmentioning

confidence: 99%

Endothelin 1 promotes osteoarthritic cartilage degradation via matrix metalloprotease 1 and matrix metalloprotease 13 induction

Roy‐Beaudry

Martel‐Pelletier

Pelletier

et al. 2003

Arthritis & Rheumatism

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Objective. Degradation of the collagenous extracellular matrix by metalloproteases (MMPs) plays an important role in the pathogenesis of osteoarthritis (OA). Recently, it was suggested that endothelin 1 (ET-1), a potent vasoconstrictor, may be involved in MMP regulation. This study investigated the role of ET-1 in OA cartilage degradation.Methods. We explored ET-1 expression and synthesis in normal and OA cartilage and synovial membrane by reverse transcription-polymerase chain reaction and immunohistochemistry. MMP-1 and MMP-13 gene expression and protein synthesis were investigated using Northern blotting and enzyme-linked immunosorbent assays. Additionally, ET-1-induced collagenase activity, type II collagen metabolites, and tissue inhibitor of metalloproteases 1 (TIMP-1) protein were evaluated.Results. We found expression and synthesis of ET-1, in situ, in both normal and OA cartilage and synovial membrane. We demonstrated that ET-1 induced gene expression and protein synthesis of both MMP-1 and MMP-13. These enzymes were produced in OA chondrocyte cultures, and the production increased in a dose-dependent manner in the presence of ET-1. In OA cartilage, ET-1 also induced type II collagenderived neoepitopes concomitantly with an increase in collagenase activity and a decrease in TIMP-1 protein.Conclusion. Our results provide strong evidence of the catabolic role of ET-1 in OA cartilage via MMP-1 and MMP-13 up-regulation. As well, ET-1 increased the net MMP/TIMP balance and secondarily increased collagen degradation. Hence, ET-1 becomes an attractive factor to target in the conception of new therapeutic approaches for OA and other diseases in which MMP-13 and MMP-1 actions are crucial in tissue alteration.

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Endothelin-1 in monolayer cultures of articular chondrocytes from young and old rats: regulation by growth factors and cytokines

Cited by 13 publications

References 34 publications

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

Effects of melatonin on the synthesis of estradiol and gene expression in pig granulosa cells

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Endothelin 1 promotes osteoarthritic cartilage degradation via matrix metalloprotease 1 and matrix metalloprotease 13 induction

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