scholarly journals Norepinephrine modulates IL-1β-induced catabolic response of human chondrocytes

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Hyun Sook Hwang ◽  
Mi Hyun Lee ◽  
Dong Jin Go ◽  
Hyun Ah Kim
Keyword(s):  
Adrenergic Receptors ◽  
Articular Chondrocytes ◽  
Explant Culture ◽  
Normal Cartilage ◽  
Cartilage Metabolism ◽  
Cartilage Explant ◽  
Catabolic Response ◽  
Β Blockers ◽  
Β Adrenergic Receptors ◽  
And Cartilage

Abstract Background The influence of the sympathetic nervous system (SNS) on metabolism of bone and cartilage expressing β-adrenergic receptors (AR) was suggested. Here, we investigated whether the SNS functions as a modulator of cartilage metabolism induced by interleukin-1beta (IL-1β). Methods Human articular chondrocytes and articular cartilage were collected from patients with osteoarthritis (OA). Chondrocyte monolayer and cartilage explant culture were stimulated with IL-1β. The activity of β-ARs was modulated by an agonist, norepinephrine (NE), and antagonists, including propranolol, atenolol, nebivolol, and nadolol. Results The levels of β1-, β2-, and β3-AR in OA cartilage and IL-1β-treated chondrocytes were lower than normal cartilage and untreated cells. Treatment of chondrocytes with IL-1β and β-blockers, including propranolol, atenolol, nebivolol, and nadolol, for 6 h significantly upregulated IL-1β-induced expression of MMP-1, -3, and − 13, compared to chondrocytes treated with IL-1β alone, indicating that antagonism of β-AR confers catabolic signals. On the other hand, NE antagonized IL-1β-induced catabolic response. In addition, NE significantly inhibited IL-1β-induced release of glycosaminoglycan (GAG) from cartilage explant culture. In addition, β-AR activity significantly affected IL-1β-stimulated phosphorylation of JNK and ERK. These results indicate that β-AR signal is associated with cartilage metabolism. Conclusions Our findings showed that β-ARs is a regulator of cartilage catabolism induced with IL-1β.

scholarly journals Norepinephrine Modulates IL-1β-induced Catabolic Response of Human Chondrocytes

2021 ◽  
Author(s):  
Hyun Sook Hwang ◽  
Mi Hyun Lee ◽  
Dong Jin Go ◽  
Hyun Ah Kim
Keyword(s):  
Adrenergic Receptors ◽  
Articular Chondrocytes ◽  
Explant Culture ◽  
Normal Cartilage ◽  
Cartilage Metabolism ◽  
Cartilage Explant ◽  
Catabolic Response ◽  
Β Blockers ◽  
Β Adrenergic Receptors ◽  
And Cartilage

Abstract BackgroundThe influence of the sympathetic nervous system (SNS) on metabolism of bone and cartilage expressing β-adrenergic receptors (AR) was suggested. Here, we investigated the relation between SNS and interleukin-1beta (IL-1β)-induced cartilage metabolism.MethodsHuman articular chondrocytes and articular cartilage were collected from patients with osteoarthritis (OA). Chondrocyte monolayer and cartilage explant culture were stimulated with IL-1β. The activity of β-ARs was modulated by an agonist, norepinephrine (NE), and antagonists, including propranolol, atenolol, nebivolol, and nadolol.ResultsThe levels of β1-, β2-, and β3-AR in OA cartilage and IL-1β-treated chondrocytes were lower than normal cartilage and untreated cells. Treatment of chondrocytes with IL-1β and β-blockers, including propranolol, atenolol, nebivolol, and nadolol, for 6 h significantly upregulated IL-1β-induced expression of MMP-1, -3, and -13, compared to chondrocytes treated with IL-1β alone, indicating that antagonism of β-AR confers catabolic signals. On the other hand, NE antagonized IL-1β-induced catabolic response. In addition, NE significantly inhibited IL-1β-induced release of glycosaminoglycan (GAG) from cartilage explant culture. In addition, β-AR activity significantly affected IL-1β-stimulated phosphorylation of JNK and ERK. These results indicate that β-AR signal is associated with cartilage metabolism.ConclusionsOur findings showed that β-ARs is a regulator of cartilage catabolism induced with IL-1β.

Three Generations of β-blockers: History, Class Differences and Clinical Applicability

2019 ◽  
Vol 15 (1) ◽  
pp. 22-31 ◽  
Author(s):  
Gabriel T. do Vale ◽  
Carla S. Ceron ◽  
Natália A. Gonzaga ◽  
Janaina A. Simplicio ◽  
Júlio C. Padovan
Keyword(s):  
Adrenergic Receptors ◽  
Cardiac Contraction ◽  
Class Differences ◽  
Beneficial Effects ◽  
Three Generations ◽  
Drug Classes ◽  
Β Blockers ◽  
Β Adrenergic Receptors ◽  
Physiological Reactions ◽  
G Protein Coupled

Background: Beta-adrenergic receptors are expressed in cardiomyocytes and activated by either noradrenaline released from sympathetic synapses or circulating catecholamines. Their corresponding receptors have three subtypes, namely, β1, β2 and β3, which are members of the G protein-coupled receptors (GPCRs) family. Activation of β1-adrenergic receptors causes various physiological reactions including cardiac contraction and renin secretion from juxtaglomerular cells of the kidney. Antagonists of β-adrenergic receptors, known as β-blockers, have been used effectively for over four decades and have beneficial effects in the treatment of cardiovascular diseases. There are three generations of β-blockers according to their pharmacological properties. Firstgeneration β-blockers are non-selective, blocking both β1- and β2-receptors; second-generation β- blockers are more cardioselective in that they are more selective for β1-receptors; and thirdgeneration β-blockers are highly selective drugs for β1-receptors. The latter also display vasodilator actions by blocking α1-adrenoreceptors and activating β3-adrenergic receptors. In addition, thirdgeneration β-blockers exhibit angiogenic, antioxidant, anti-proliferative, anti-hypertrophic and antiapoptotic activities among other effects that are still under investigation. Conclusion: The objective of this review is to describe the evolution observed during the development of the three distinctive generations, thereby highlighting the advantages of third-generation β- blockers over the other two drug classes.

scholarly journals Control of cytokinesis by β-adrenergic receptors indicates an approach for regulating cardiomyocyte endowment

2019 ◽  
Author(s):  
Honghai Liu ◽  
Cheng-Hai Zhang ◽  
Niyatie Ammanamanchi ◽  
Sangita Suresh ◽  
Christopher Lewarchik ◽  
...  
Keyword(s):  
Heart Failure ◽  
Adrenergic Receptors ◽  
Transcriptional Profiling ◽  
Pulmonary Stenosis ◽  
Underlying Mechanism ◽  
Developing Heart ◽  
The Us ◽  
Β Blocker ◽  
Β Blockers ◽  
Β Adrenergic Receptors

ABSTRACT/SUMMARYOne million patients with congenital heart disease (CHD) live in the US. They have a lifelong risk of developing heart failure. Current concepts do not sufficiently address mechanisms of heart failure development specifically for these patients. We show that cardiomyocyte cytokinesis failure is increased in tetralogy of Fallot with pulmonary stenosis (ToF/PS), a common form of CHD. Labeling of a ToF/PS baby with isotope-tagged thymidine showed cytokinesis failure after birth. We used single-cell transcriptional profiling to discover that the underlying mechanism is repression of the cytokinesis gene ECT2, and show that this is downstream of β-adrenergic receptors (β-AR). Inactivation of the β-AR genes and administration of the β-blocker propranolol increased cardiomyocyte division in neonatal mice, which increased the endowment and conferred benefit after myocardial infarction in adults. Propranolol enabled the division of ToF/PS cardiomyocytes. These results suggest that β-blockers should be evaluated for increasing cardiomyocyte division in patients with ToF/PS and other types of CHD.

scholarly journals Water Matters: Role of Water in the Binding Selectivity of β-Blockers to Human β-Adrenergic Receptors

2013 ◽  
Vol 104 (2) ◽  
pp. 405a
Author(s):  
Karol Kaszuba ◽  
MIkko Karttunen ◽  
Ilpo Vattulainen ◽  
Tomasz Rog
Keyword(s):  
Adrenergic Receptors ◽  
Binding Selectivity ◽  
Β Blockers ◽  
Β Adrenergic Receptors

scholarly journals β-Adrenergic Receptors and cAMP Response Increase during Explant Culture of Human Fetal Lung: Partial Inhibition by Dexamethasone

1990 ◽  
Vol 28 (3) ◽  
pp. 190-195 ◽  
Author(s):  
Deborah J Davis ◽  
Mark M Jacobs ◽  
Philip L Ballard ◽  
Linda K Gonzales ◽  
James M Roberts
Keyword(s):  
Adrenergic Receptors ◽  
Fetal Lung ◽  
Explant Culture ◽  
Partial Inhibition ◽  
Response Increase ◽  
Β Adrenergic Receptors ◽  
Human Fetal Lung

Molecular Docking and Drug Discovery in β-Adrenergic Receptors

2017 ◽  
Vol 24 (39) ◽  
Author(s):  
Santiago Vilar ◽  
Eduardo Sobarzo-Sanchez ◽  
Lourdes Santana ◽  
Eugenio Uriarte
Keyword(s):  
Molecular Docking ◽  
Drug Discovery ◽  
Adrenergic Receptors ◽  
Β Adrenergic Receptors

scholarly journals Metabolic Syndrome Predisposes to Osteoarthritis: Lessons from Model System

Cartilage ◽  
2020 ◽  
pp. 194760352098016
Author(s):  
Sampath Samuel Joshua Pragasam ◽  
Vijayalakshmi Venkatesan
Keyword(s):  
Subchondral Bone ◽  
Fat Mass ◽  
Articular Chondrocytes ◽  
Bone Cyst ◽  
Primary Cultures ◽  
Abdominal Circumference ◽  
Enzyme Linked Immunosorbent Assay ◽  
Micro Ct ◽  
Tnf Α ◽  
And Cartilage

Objective The present study aims to assess for temporal changes in tibial subchondral bone and cartilage in WNIN/Gr-Ob rats (portraying obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, hypertension) in comparison with Wistar controls (WNIN) using anthropometry, micro-computed tomography (micro-CT), scanning electron microscopy (SEM), histopathology, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Design Body weight, abdominal circumference, body mass index (BMI), lean/fat mass, serum tumor necrosis factor (TNF)-α levels were measured (ELISA), followed by ultrastructural analysis of tibial subchondral bone (micro-CT) and cartilage architecture (histopathology and SEM) in WNIN/Gr-Ob and WNIN rats with age (3, 6 and 9 months). Additionally, primary cultures of articular chondrocytes isolated from 6-month-old WNIN/Gr-Ob and WNIN rats were assessed for matrix metalloproteinase (MMP)-13 and Collagen type II (COL2A1) by immunofluorescence. Results WNIN/Gr-Ob rats exhibited frank obesity with increased BMI, lean and fat mass vis-à-vis significantly higher levels of serum TNF-α (6>9>3 months) as compared with the controls. With an increase in BMI, WNIN/Gr-Ob rats presented with tibial cartilage fibrillation, erosion, osteophyte formation (6 months) and subchondral bone cyst (9 months) confirmed by histology and SEM. An increase in subchondral trabecular bone volume (sclerosis with decreased plate porosity) was observed in all ages in WNIN/Gr-Ob rats compared to their Control. Gaining insights, primary cultures of articular chondrocytes complemented with altered cellular expressions of COL2A1 and MMP-13 from WNIN/Gr-Ob rats, indicating osteoarthritis (OA) progression. Conclusion Multiple metabolic perturbations featured in WNIN/Gr-Ob rats were effective to induce spontaneous OA-like degenerative changes affecting knee joints akin to human OA.

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