Effects of AURKA‐mediated degradation of SOD2 on mitochondrial dysfunction and cartilage homeostasis in osteoarthritis

2019 ◽  
Vol 234 (10) ◽  
pp. 17727-17738 ◽  
Author(s):  
Cheng Yang ◽  
Di You ◽  
Jun Huang ◽  
Bo Yang ◽  
Xianzhe Huang ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cartilage Homeostasis ◽  
And Cartilage

Adenosinergic signalling in chondrogenesis and cartilage homeostasis: Friend or foe?

2020 ◽  
Vol 174 ◽  
pp. 113784 ◽  
Author(s):  
Rui Pinto-Cardoso ◽  
Flávio Pereira-Costa ◽  
João Pedro Faria ◽  
Patrícia Bandarrinha ◽  
Catarina Bessa-Andrês ◽  
...  
Keyword(s):  
Cartilage Homeostasis ◽  
And Cartilage

scholarly journals Follistatin Alleviates Synovitis and Articular Cartilage Degeneration Induced by Carrageenan

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jun Yamada ◽  
Kunikazu Tsuji ◽  
Kazumasa Miyatake ◽  
Yu Matsukura ◽  
Kahaer Abula ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Proinflammatory Cytokines ◽  
Synovial Membrane ◽  
Joint Inflammation ◽  
Cartilage Degeneration ◽  
Decoy Receptor ◽  
Arthritis Model ◽  
Cartilage Homeostasis ◽  
Articular Cartilage Degeneration ◽  
And Cartilage

Activins are proinflammatory cytokines which belong to the TGFβsuperfamily. Follistatin is an extracellular decoy receptor for activins. Since both activins and follistatin are expressed in articular cartilage, we hypothesized that activin-follistatin signaling participates in the process of joint inflammation and cartilage degeneration. To test this hypothesis, we examined the effects of follistatin in a carrageenan-induced mouse arthritis model. Synovitis induced by intra-articular injection of carrageenan was significantly alleviated by preinjection with follistatin. Macrophage infiltration into the synovial membrane was significantly reduced in the presence of follistatin. In addition, follistatin inhibited proteoglycan erosion induced by carrageenan in articular cartilage. These data indicate that activin-follistatin signaling is involved in joint inflammation and cartilage homeostasis. Our data suggest that follistatin can be a new therapeutic target for inflammation-induced articular cartilage degeneration.

scholarly journals YAP/TAZ in Bone and Cartilage Biology

2022 ◽  
Vol 9 ◽  
Author(s):  
Mylène Zarka ◽  
Eric Haÿ ◽  
Martine Cohen-Solal
Keyword(s):  
Cell Fate ◽  
Bone Biology ◽  
Organ Growth ◽  
Cellular Models ◽  
Cartilage Homeostasis ◽  
Cartilage Biology ◽  
Cartilage Cells ◽  
And Function ◽  
And Cartilage

YAP and TAZ were initially described as the main regulators of organ growth during development and more recently implicated in bone biology. YAP and TAZ are regulated by mechanical and cytoskeletal cues that lead to the control of cell fate in response to the cellular microenvironment. The mechanical component represents a major signal for bone tissue adaptation and remodelling, so YAP/TAZ contributes significantly in bone and cartilage homeostasis. Recently, mice and cellular models have been developed to investigate the precise roles of YAP/TAZ in bone and cartilage cells, and which appear to be crucial. This review provides an overview of YAP/TAZ regulation and function, notably providing new insights into the role of YAP/TAZ in bone biology.

scholarly journals Adipokine Contribution to the Pathogenesis of Osteoarthritis

2017 ◽  
Vol 2017 ◽  
pp. 1-26 ◽  
Author(s):  
Daniel Azamar-Llamas ◽  
Gabriela Hernández-Molina ◽  
Bárbara Ramos-Ávalos ◽  
Janette Furuzawa-Carballeda
Keyword(s):  
Adipose Tissue ◽  
Risk Factor ◽  
Weight Bearing ◽  
Epidemiological Studies ◽  
Overweight And Obesity ◽  
Cartilage Explants ◽  
Metabolic Factors ◽  
Physiological Mechanisms ◽  
Cartilage Homeostasis ◽  
And Cartilage

Recent studies have shown that overweight and obesity play an important role in the development of osteoarthritis (OA). However, joint overload is not the only risk factor in this disease. For instance, the presence of OA in non-weight-bearing joints such as the hand suggests that metabolic factors may also contribute to its pathogenesis. Recently, white adipose tissue (WAT) has been recognized not only as an energy reservoir but also as an important secretory organ of adipokines. In this regard, adipokines have been closely associated with obesity and also play an important role in bone and cartilage homeostasis. Furthermore, drugs such as rosuvastatin or rosiglitazone have demonstrated chondroprotective and anti-inflammatory effects in cartilage explants from patients with OA. Thus, it seems that adipokines are important factors linking obesity, adiposity, and inflammation in OA. In this review, we are focused on establishing the physiological mechanisms of adipokines on cartilage homeostasis and evaluating their role in the pathophysiology of OA based on evidence derived from experimental research as well as from clinical-epidemiological studies.

scholarly journals MicroRNAs’ Involvement in Osteoarthritis and the Prospects for Treatments

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Xiao-Ming Yu ◽  
Hao-Ye Meng ◽  
Xue-Ling Yuan ◽  
Yu Wang ◽  
Quan-Yi Guo ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Target Genes ◽  
Noncoding Rnas ◽  
Genetic Changes ◽  
Future Studies ◽  
Small Noncoding Rnas ◽  
Cartilage Homeostasis ◽  
Target Binding ◽  
And Cartilage

Osteoarthritis (OA) is a chronic disease and its etiology is complex. With increasing OA incidence, more and more people are facing heavy financial and social burdens from the disease. Genetics-related aspects of OA pathogenesis are not well understood. Recent reports have examined the molecular mechanisms and genes related to OA. It has been realized that genetic changes in articular cartilage and bone may contribute to OA’s development. Osteoclasts, osteoblasts, osteocytes, and chondrocytes in joints must express appropriate genes to achieve tissue homeostasis, and errors in this can cause OA. MicroRNAs (miRNAs) are small noncoding RNAs that have been discovered to be overarching regulators of gene expression. Their ability to repress many target genes and their target-binding specificity indicate a complex network of interactions, which is still being defined. Many studies have focused on the role of miRNAs in bone and cartilage and have identified numbers of miRNAs that play important roles in regulating bone and cartilage homeostasis. Those miRNAs may also be involved in the pathology of OA, which is the focus of this review. Future studies on the role of miRNAs in OA will provide important clues leading to a better understanding of the mechanism(s) of OA and, more particularly, to the development of therapeutic targets for OA.

scholarly journals A new prescription for growth? Statins, cholesterol and cartilage homeostasis

2015 ◽  
Vol 23 (4) ◽  
pp. 503-506 ◽  
Author(s):  
J.R. Bush ◽  
N.G. Bérubé ◽  
F. Beier
Keyword(s):  
Cartilage Homeostasis ◽  
And Cartilage

scholarly journals Mitochondrial dysfunction triggers a catabolic response in chondrocytes via ROS-mediated activation of the JNK/AP1 pathway

2020 ◽  
Vol 133 (22) ◽  
pp. jcs247353 ◽  
Author(s):  
Mohammad Y. Ansari ◽  
Nashrah Ahmad ◽  
Sriharsha Voleti ◽  
Saima J. Wase ◽  
Kimberly Novak ◽  
...  
Keyword(s):  
Mitochondrial Dysfunction ◽  
Cartilage Explants ◽  
Activator Protein 1 ◽  
Induced Expression ◽  
Mitochondrial Superoxide ◽  
Catabolic Genes ◽  
Catabolic Response ◽  
Cox 2 ◽  
Nfκb Pathway ◽  
And Cartilage

ABSTRACTMitochondrial function is impaired in osteoarthritis (OA) but its impact on cartilage catabolism is not fully understood. Here, we investigated the molecular mechanism of mitochondrial dysfunction-induced activation of the catabolic response in chondrocytes. Using cartilage slices from normal and OA cartilage, we showed that mitochondrial membrane potential was lower in OA cartilage, and that this was associated with increased production of mitochondrial superoxide and catabolic genes [interleukin 6 (IL-6), COX-2 (also known as PTGS2), MMP-3, -9, -13 and ADAMTS5]. Pharmacological induction of mitochondrial dysfunction in chondrocytes and cartilage explants using carbonyl cyanide 3-chlorophenylhydrazone increased mitochondrial superoxide production and the expression of IL-6, COX-2, MMP-3, -9, -13 and ADAMTS5, and cartilage matrix degradation. Mitochondrial dysfunction-induced expression of catabolic genes was dependent on the JNK (herein referring to the JNK family)/activator protein 1 (AP1) pathway but not the NFκB pathway. Scavenging of mitochondrial superoxide with MitoTEMPO, or pharmacological inhibition of JNK or cFos and cJun, blocked the mitochondrial dysfunction-induced expression of the catabolic genes in chondrocytes. We demonstrate here that mitochondrial dysfunction contributes to OA pathogenesis via JNK/AP1-mediated expression of catabolic genes. Our data shows that AP1 could be used as a therapeutic target for OA management.This article has an associated First Person interview with the first author of the paper.

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