Endothelin-1 receptors on cultured rat articular chondrocytes: regulation by age, growth factors, and cytokines, and effect on cAMP production

Messai, Habib; Panasyuk, Andrei; Khatib, Abdel‐Majid; Barbara, A.; Mitrović, D

doi:10.1016/s0047-6374(01)00231-7

Cited by 11 publications

(14 citation statements)

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“…Importantly, this was correlated with an increased ET-1 levels in the culture medium, as determined by western blotting, after 36 h of incubation. This is in line with previous reports that ET-1 production is increased and regulated by growth factors and cytokines such as IL-1ß, TNF-α, LPS, TGF- ß1, EGF, and IGF-I in rat articular chondrocytes [30]. The biologic effect of one cytokine is often modified or augmented by another, but the exact mechanisms are still unclear.…”

Section: Discussionsupporting

confidence: 92%

Association of Endothelin-1 Expression and Cartilaginous Endplate Degeneration in Humans

et al. 2013

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BackgroundInflammatory cytokines are involved in intervertebral disc (IVD) degeneration. Endothelin-1 (ET-1), a 21-amino-acid cytokine implicated with cartilage degradation, is secreted by vascular endothelial cells and also by many other cell types. The expression of ET-1 in human IVD cartilage endplate (CEP) and its role in disc degeneration have not been explored.Methods and FindingsThe expression of ET-1 in degenerated CEP was analyzed by immunohistochemical staining and Western blotting; ET-1 was demonstrated in cartilaginous endplate cells (CECs) by immunofluorescent staining. The ET-1 mRNA expression and protein production by CECs stimulated by tumor necrosis factor alpha (TNF-α), a pro-inflammatory cytokine, were determined by real-time PCR analysis and Western blotting, respectively. The matrix metalloprotease-1 (MMP-1), MMP-13 and tissue inhibitor of metalloproteases-1 (TIMP-1) levels in the supernatant of cultured CECs treated with ET-1 were determined using enzyme-linked immunosorbent assays. Nitric oxide (NO) release and nitric oxide synthase (NOS) activity were measured using a spectrophotometric assay. The apoptosis of CECs by ET-1 was measured by an Annexin V-FITC detection assay. The production of ET-1 in degenerated cartilage endplate was significantly higher than normal CEP. The results showed that ET-1 was expressed by CECs and modulated by TNF-α in a dose-dependent manner. ET-1 increased production of MMP-1 and MMP-13, decreased TIMP-1 production, and induced NO and NOS release by cultured CECs. The direct stimulation of CECs by ET-1 did not promote cell apoptosis.ConclusionThe study results suggest that ET-1 played a pivotal role in human CEP degeneration, and may be a new target for development of therapies for this condition.

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Section: Discussionsupporting

confidence: 92%

Association of Endothelin-1 Expression and Cartilaginous Endplate Degeneration in Humans

et al. 2013

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“…A previous study had demonstrated that FGF stimulates the proliferation of fibroblasts and induces the synthesis of plasminogen and collagen by adjusting the proliferation and migration of endothelial cells [46]. An antibody against FGF-2, a member of the FGF family, was administered continuously for 4 weeks in the knee joint of rabbits, and the results showed that the angles of the flexion contracture and the total collagen content of the adhesion tissue were lower in the FGF-2 antibody administration group compared with the control group.…”

Section: Discussionmentioning

confidence: 99%

Reduction of adhesion formation after knee surgery in a rat model by botulinum toxin A

Gao

Liu

et al. 2017

Bioscience Reports

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Adhesion of the knee is a major concern after knee surgery, the treatment of which is difficult. Botulinum toxin A (BTX-A) injection is demonstrated as efficient in treating knee adhesion after surgery. However, the treatment outcomes and the mechanism of action are not yet determined. The aim of the present study was to examine the effects and molecular mechanism of a BTX-A treatment in preventing adhesion of the knee. Twenty-four Wistar rats were randomly divided into a BTX-A treatment group and a control group. BTX-A or saline was injected into the cavity of the knee in the BTX-A treatment or control group respectively. Gross and histopathological examinations of interleukin 1 (IL-1) and fibroblast growth factor (FGF) levels, as well as fibroblast cell numbers, were assessed in the knee intra-articular adhesions in each group 6 weeks after recovery from the surgery. Macroscopic observations showed a significant reduction in adhesion severity in the BTX-A treatment group compared with the control group. In addition, the levels of IL-1 and FGF were lower and the number of fibroblasts was smaller in the BTX-A treatment group compared with those in the control group. BTX-A prevented intra-articular adhesion of knee in the rats, which might be associated with reduced expressions of IL-1 and FGF.

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“…ET-1 also causes excessive production of nitric oxide, which is generated as the result of an increase in inducible nitric oxide synthase levels [9]. These effects occur mainly via endothelin receptor type A (ETA) [10]: it is expressed in articular tissue by chondrocytes, synoviocytes, and endothelial cells, where it plays a significant role in cartilage and bone metabolism [11,12]; ETA also potentiates inflammatory joint pain induced by ET-1 [13,14]. …”

Section: Introductionmentioning

confidence: 99%

Nociceptive tolerance is improved by bradykinin receptor B1 antagonism and joint morphology is protected by both endothelin type A and bradykinin receptor B1 antagonism in a surgical model of osteoarthritis

et al. 2011

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IntroductionEndothelin-1, a vasoconstrictor peptide, influences cartilage metabolism mainly via endothelin receptor type A (ETA). Along with the inflammatory nonapeptide vasodilator bradykinin (BK), which acts via bradykinin receptor B1 (BKB1) in chronic inflammatory conditions, these vasoactive factors potentiate joint pain and inflammation. We describe a preclinical study of the efficacy of treatment of surgically induced osteoarthritis with ETA and/or BKB1 specific peptide antagonists. We hypothesize that antagonism of both receptors will diminish osteoarthritis progress and articular nociception in a synergistic manner.MethodsOsteoarthritis was surgically induced in male rats by transection of the right anterior cruciate ligament. Animals were subsequently treated with weekly intra-articular injections of specific peptide antagonists of ETA and/or BKB1. Hind limb nociception was measured by static weight bearing biweekly for two months post-operatively. Post-mortem, right knee joints were analyzed radiologically by X-ray and magnetic resonance, and histologically by the OARSI histopathology assessment system.ResultsSingle local BKB1 antagonist treatment diminished overall hind limb nociception, and accelerated post-operative recovery after disease induction. Both ETA and/or BKB1 antagonist treatments protected joint radiomorphology and histomorphology. Dual ETA/BKB1 antagonism was slightly more protective, as measured by radiology and histology.ConclusionsBKB1 antagonism improves nociceptive tolerance, and both ETA and/or BKB1 antagonism prevents joint cartilage degradation in a surgical model of osteoarthritis. Therefore, they represent a novel therapeutic strategy: specific receptor antagonism may prove beneficial in disease management.

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Endothelin-1 receptors on cultured rat articular chondrocytes: regulation by age, growth factors, and cytokines, and effect on cAMP production

Cited by 11 publications

References 30 publications

Association of Endothelin-1 Expression and Cartilaginous Endplate Degeneration in Humans

Association of Endothelin-1 Expression and Cartilaginous Endplate Degeneration in Humans

Reduction of adhesion formation after knee surgery in a rat model by botulinum toxin A

Nociceptive tolerance is improved by bradykinin receptor B1 antagonism and joint morphology is protected by both endothelin type A and bradykinin receptor B1 antagonism in a surgical model of osteoarthritis

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