Hypotonic stress promotes ATP release, reactive oxygen species production and cell proliferation via TRPV4 activation in rheumatoid arthritis rat synovial fibroblasts

Hu, Fang; Hui, Zhenhai; Wei, Wei; Yang, Jianyu; Chen, Ziyuan; Guo, Bu; Xing, Fu-qi; Zhang, Xinzheng; Pan, Leiting; Xu, Jingyi

doi:10.1016/j.bbrc.2017.03.008

Cited by 24 publications

(17 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…An increase of ATP concentration in bovine synovial fluid has also been observed in osteoarthritis, sodium urate-induced synovitis in dogs [33], and in arthritis induced in rats [52]. Therefore, extracellular ATP concentrations are nowadays considered as important pro-inflammatory agents [53].…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Pro-inflammatory mediators and neutrophils are increased in synovial fluid from heifers with acute ruminal acidosis

et al. 2019

View full text Add to dashboard Cite

Background Acute ruminal acidosis (ARA) is a metabolic disease of cattle characterized by an aseptic synovitis. ARA is the result of an increased intake of highly fermentable carbohydrates that frequently occurs in dairy cattle subjected to high production requirements. In human joint diseases such as rheumatoid arthritis and gout, several pro-inflammatory molecules are increased in the synovial fluid, including cytokines, prostaglandin E 2 (PGE 2 ), metalloproteinases, and neutrophil extracellular traps (NETs). The aim of this study was to identify the presence of proinflammatory mediators and neutrophils in the synovial fluid of heifers with ARA, induced by an oligofructose overload. Five heifers were challenged with an oligofructose overload (13 g/kg BW) dissolved in water. As a control, a similar vehicle volume was used in four heifers. Synovial fluid samples were collected from the tarso-crural joint and PGE 2 , IL-6, IL-1β, ATP, lactate dehydrogenase (LDH), albumin, glucose, matrix metalloproteinase-9 (MMP-9), cellular free DNA, NETs, and serpin B1 were analyzed at 0, 9, and 24 h post treatment. Results At 9 h post oligofructose overload, an increase of IL-1β, IL-6, PGE 2 , serpin B1 and LDH was detected in the joints when compared to the control group. At 24 h, the synovial fluid was yellowish, viscous, turbid, and contained abundant neutrophils. An increase of DNA-backbone-like traps, histone 3 (H 3 cit), aggregated neutrophil extracellular traps ( agg NETs), and serpin B1 were observed 24 h post treatment. Furthermore, albumins, LDH, ATP, MMP-9, IL-6, and IL-1β were increased after 24 h. Conclusions The overall results indicate that IL-1β, IL-6 and PGE 2 , were the earliest proinflammatory parameters that increased in the synovial fluid of animals with ARA. Furthermore, the most sever inflammatory response in the joint was observed after 24 h and could be associated with a massive presence of neutrophils and release of agg NETs. Electronic supplementary material The online version of this article (10.1186/s12917-019-1974-x) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Therefore, extracellular ATP concentrations are nowadays considered as important pro-inflammatory agents [53]. Since ATP was observed at 24 h, this suggests that either neutrophils [54, 55] or synovium [52] can contribute to the release of ATP into the joint.…”

Section: Discussionmentioning

confidence: 99%

Pro-inflammatory mediators and neutrophils are increased in synovial fluid from heifers with acute ruminal acidosis

et al. 2019

View full text Add to dashboard Cite

show abstract

“…UTP and ATP activate calcium-mobilising P2UR to synergistically act with IL-1 to stimulate release of prostaglandin E 2 from human rheumatoid synovial cells. Hypotonic stress promotes ATP release and cell proliferation via transient receptor potential vanilloid 4 activation in RA rat synovial fibroblasts ( Hu et al, 2017 ).…”

Section: Musculoskeletal Diseasesmentioning

confidence: 99%

Purinergic Signalling: Therapeutic Developments

2017

View full text Add to dashboard Cite

Purinergic signalling, i.e., the role of nucleotides as extracellular signalling molecules, was proposed in 1972. However, this concept was not well accepted until the early 1990’s when receptor subtypes for purines and pyrimidines were cloned and characterised, which includes four subtypes of the P1 (adenosine) receptor, seven subtypes of P2X ion channel receptors and 8 subtypes of the P2Y G protein-coupled receptor. Early studies were largely concerned with the physiology, pharmacology and biochemistry of purinergic signalling. More recently, the focus has been on the pathophysiology and therapeutic potential. There was early recognition of the use of P1 receptor agonists for the treatment of supraventricular tachycardia and A2A receptor antagonists are promising for the treatment of Parkinson’s disease. Clopidogrel, a P2Y12 antagonist, is widely used for the treatment of thrombosis and stroke, blocking P2Y12 receptor-mediated platelet aggregation. Diquafosol, a long acting P2Y2 receptor agonist, is being used for the treatment of dry eye. P2X3 receptor antagonists have been developed that are orally bioavailable and stable in vivo and are currently in clinical trials for the treatment of chronic cough, bladder incontinence, visceral pain and hypertension. Antagonists to P2X7 receptors are being investigated for the treatment of inflammatory disorders, including neurodegenerative diseases. Other investigations are in progress for the use of purinergic agents for the treatment of osteoporosis, myocardial infarction, irritable bowel syndrome, epilepsy, atherosclerosis, depression, autism, diabetes, and cancer.

show abstract

“…ATP release into the synovial fluid is triggered by the hypoxic environment in the synovium and hypotonic nature of the synovial fluid typical of RA. When synoviocytes in vitro were challenged with a hypotonic shock they activated a mechanism of calcium-mediated ATP release leading to reduced cell viability and synovium membrane hyperplasia (Hu et al, 2017). A study in 28 OA patients demonstrated that ATP concentration in the synovial fluid positively correlates with pain experienced by the patients.…”

Section: P2 Receptorsmentioning

confidence: 99%

Signaling of the Purinergic System in the Joint

Corciulo

Cronstein

2020

Front. Pharmacol.

View full text Add to dashboard Cite

The joint is a complex anatomical structure consisting of different tissues, each with a particular feature, playing together to give mobility and stability at the body. All the joints have a similar composition including cartilage for reducing the friction of the movement and protecting the underlying bone, a synovial membrane that produces synovial fluid to lubricate the joint, ligaments to limit joint movement, and tendons for the interaction with muscles. Direct or indirect damage of one or more of the tissues forming the joint is the foundation of different pathological conditions. Many molecular mechanisms are involved in maintaining the joint homeostasis as well as in triggering disease development. The molecular pathway activated by the purinergic system is one of them.The purinergic signaling defines a group of receptors and intermembrane channels activated by adenosine, adenosine diphosphate, adenosine 5'-triphosphate, uridine triphosphate, and uridine diphosphate. It has been largely described as a modulator of many physiological and pathological conditions including rheumatic diseases. Here we will give an overview of the purinergic system in the joint describing its expression and function in the synovium, cartilage, ligament, tendon, and bone with a therapeutic perspective.

show abstract

Hypotonic stress promotes ATP release, reactive oxygen species production and cell proliferation via TRPV4 activation in rheumatoid arthritis rat synovial fibroblasts

Cited by 24 publications

References 28 publications

Pro-inflammatory mediators and neutrophils are increased in synovial fluid from heifers with acute ruminal acidosis

Pro-inflammatory mediators and neutrophils are increased in synovial fluid from heifers with acute ruminal acidosis

Purinergic Signalling: Therapeutic Developments

Signaling of the Purinergic System in the Joint

Contact Info

Product

Resources

About