Production of endothelin-1 by cultured human synoviocytes

Yoshida, Hiroshi; Ohhara, Morihiro; Ohsumi, Kazuoki

doi:10.1016/s0009-8981(96)06475-3

Cited by 5 publications

(2 citation statements)

References 4 publications

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“…This is in accordance with reported findings in RA synovial fluid where elevated ET-1 levels were found [8]. The major source is most likely macrophage-like synoviocytes [8,9]. When the present results are compared with our previous findings the ET-1-LI curve almost perfectly matches the vascular inflammatory response [1].…”

Section: Et-1-lisupporting

confidence: 93%

Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the course of antigen-induced arthritis in the rat

Andersson¹,

Lexmuller²,

Alving

et al. 1999

Inflamm. res.

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Section: Et-1-lisupporting

confidence: 93%

Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the course of antigen-induced arthritis in the rat

Andersson¹,

Lexmuller²,

Alving

et al. 1999

Inflamm. res.

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“…Local production of ET‐1 in human synovial membranes was previously reported by Miyasaka et al (30), who observed an ET‐like immunoreactivity that was many times higher in synovial fluid than in plasma. It has also been shown that ET‐1 is present in macrophage‐like type A cells in cultured synovial fluid from RA patients (29, 38). Here we confirmed these findings and showed that ET‐1 was also produced by articular chondrocytes.…”

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 inhibits size dependent lymphatic clearance of PEG-based conjugates after intra-articular injection into the rat knee

et al. 2019

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Production of endothelin-1 by cultured human synoviocytes

Cited by 5 publications

References 4 publications

Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the course of antigen-induced arthritis in the rat

Periarticular tissue levels of cytokine- and endothelin-1-like immunoreactivity during the course of antigen-induced arthritis in the rat

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

Endothelin-1 inhibits size dependent lymphatic clearance of PEG-based conjugates after intra-articular injection into the rat knee

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