scholarly journals Genetics in Osteoarthritis Knee

2021 ◽  
Author(s):  
Rajeshwar Nath Srivastava ◽  
Amar Chandra Sharma ◽  
Sudeepti Ratan Srivastava ◽  
Saloni Raj ◽  
Lavini Raj
Keyword(s):  
Articular Cartilage ◽  
Genetic Background ◽  
Drug Targets ◽  
Essential Role ◽  
Gene Interaction ◽  
Disease Pathogenesis ◽  
Osteoarthritis Knee ◽  
Gene Functions ◽  
Joint Disorder

Osteoarthritis (OA) is a debilitating joint disorder with a complex pathogeny wherein diverse factors interact, causing a process of deterioration of the articular cartilage and the subchondral bone. It can be primary or secondary but has common clinical, radiological, and pathological manifestations. Unfortunately, there are no curative or preventive options available for this disease. The knee is the most common site to develop OA among all synovial joints. Both environmental and genetic factors play an essential role in the initiation of the disease. Identifying the genes underlying the genetic background could give new insights into the pathophysiology of knee osteoarthritis (KOA) and could potentially lead to new drug targets. Several genes involving developmental processes or maintenance of cartilage and bone are found to be associated with KOA susceptibility and progression. Understanding the gene functions has improved the knowledge towards the disease pathogenesis. So, it will be of interest to investigate the role of gene-gene interaction in the disease.

scholarly journals Up-regulation of P21-activated kinase 1 in osteoarthritis chondrocytes is responsible for osteoarthritic cartilage destruction

2020 ◽  
Vol 40 (1) ◽  
Author(s):  
Wanli Ma ◽  
Xiaohe Wang ◽  
Chunhui Wang ◽  
Mingzhi Gong ◽  
Peng Ren
Keyword(s):  
Articular Cartilage ◽  
Cartilage Destruction ◽  
Related Factors ◽  
Osteoarthritic Cartilage ◽  
Resident Cell ◽  
Joint Disorder ◽  
Osteoarthritis Chondrocytes ◽  
P21 Activated Kinase ◽  
Pak1 Expression

Abstract Osteoarthritis is mainly caused by a degenerative joint disorder, which is characterized by the gradual degradation of articular cartilage and synovial inflammation. The chondrocyte, the unique resident cell type of articular cartilage, is crucial for the development of osteoarthritis. Previous studies revealed that P21-activated kinase-1 (PAK1) was responsible for the initiation of inflammation. The purpose of the present study was to determine the potential role of PAK1 in osteoarthritis. The level of PAK1 expression was measured by Western blot and quantitative real-time PCR in articular cartilage from osteoarthritis model rats and patients with osteoarthritis. In addition, the functional role of aberrant PAK1 expression was detected in the chondrocytes. We found that the expression of PAK1 was significantly increased in chondrocytes treated with osteoarthritis-related factors. Increased expression of PAK1 was also observed in knee articular cartilage samples from patients with osteoarthritis and osteoarthritis model rats. PAK1 was found to inhibit chondrocytes proliferation and to promote the production of inflammatory cytokines in cartilages chondrocytes. Furthermore, we found that PAK1 modulated the production of extracellular matrix and cartilage degrading enzymes in chondrocytes. Results of the present studies demonstrated that PAK1 might play an important role in the pathogenesis of osteoarthritis.

scholarly journals Recent Advances in Understanding the Role of Cartilage Lubrication in Osteoarthritis

Molecules ◽  
2021 ◽  
Vol 26 (20) ◽  
pp. 6122
Author(s):  
Yumei Li ◽  
Zhongrun Yuan ◽  
Hui Yang ◽  
Haijian Zhong ◽  
Weijie Peng ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Essential Role ◽  
Daily Life ◽  
Early Stage ◽  
Joint Disease ◽  
Low Friction ◽  
Cartilage Surface ◽  
Wear And Tear ◽  
Lubrication Properties

The remarkable lubrication properties of normal articular cartilage play an essential role in daily life, providing almost frictionless movements of joints. Alterations of cartilage surface or degradation of biomacromolecules within synovial fluid increase the wear and tear of the cartilage and hence determining the onset of the most common joint disease, osteoarthritis (OA). The irreversible and progressive degradation of articular cartilage is the hallmark of OA. Considering the absence of effective options to treat OA, the mechanosensitivity of chondrocytes has captured attention. As the only embedded cells in cartilage, the metabolism of chondrocytes is essential in maintaining homeostasis of cartilage, which triggers motivations to understand what is behind the low friction of cartilage and develop biolubrication-based strategies to postpone or even possibly heal OA. This review firstly focuses on the mechanism of cartilage lubrication, particularly on boundary lubrication. Then the mechanotransduction (especially shear stress) of chondrocytes is discussed. The following summarizes the recent development of cartilage-inspired biolubricants to highlight the correlation between cartilage lubrication and OA. One might expect that the restoration of cartilage lubrication at the early stage of OA could potentially promote the regeneration of cartilage and reverse its pathology to cure OA.

c-Jun N-terminal kinase – c-Jun pathway transactivates Bim to promote osteoarthritis

2014 ◽  
Vol 92 (2) ◽  
pp. 132-139 ◽  
Author(s):  
Zhiqiang Ye ◽  
Yuxian Chen ◽  
Rongkai Zhang ◽  
Haitao Dai ◽  
Chun Zeng ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Articular Cartilage ◽  
Rna Interference ◽  
Animal Models ◽  
Chondrocyte Apoptosis ◽  
Kinase C ◽  
Tnf Α ◽  
Chemical Inhibitors ◽  
Joint Disorder

Osteoarthritis (OA) is a chronic degenerative joint disorder. Previous studies have shown abnormally increased apoptosis of chondrocytes in patients and animal models of OA. TNF-α and nitric oxide have been reported to induce chondrocyte ageing; however, the mechanism of chondrocyte apoptosis induced by IL-1β has remained unclear. The aim of this study is to identify the role of the c-Jun N-terminal kinase (JNK) – c-Jun pathway in regulating induction of Bim, and its implication in chondrocyte apoptosis. This study showed that Bim is upregulated in chondrocytes obtained from the articular cartilage of OA patients and in cultured mouse chondrocytes treated with IL-1β. Upregulation of Bim was found to be critical for chondrocyte apoptosis induced by IL-1β, as revealed by the genetic knockdown of Bim, wherein apoptosis was greatly reduced in the chondrocytes. Moreover, activation of the JNK–c-Jun pathway was observed under IL-1β treatment, as indicated by the increased expression levels of c-Jun protein. Suppression of the JNK–c-Jun pathway, using chemical inhibitors and RNA interference, inhibited the Bim upregulation induced by IL-1β. These findings suggest that the JNK–c-Jun pathway is involved in the upregulation of Bim during OA and that the JNK–c-Jun–Bim pathway is vital for chondrocyte apoptosis.

scholarly journals Microbial endophytes: an untapped resource with antitumor and anti-microbial properties

2020 ◽  
pp. 9-20
Author(s):  
Preetinder Kaur ◽  
Gurpreet Kaur
Keyword(s):  
Medicinal Plants ◽  
Drug Targets ◽  
Essential Role ◽  
Antimicrobial Agents ◽  
Symbiotic Association ◽  
Clinical Grade ◽  
Microbial Infections ◽  
Hostile Environments ◽  
Untapped Resource

Endophytes (mostly fungi and bacteria) are the microorganisms living in close symbiotic association with plants. Endophytes growing within medicinal plants in hostile environments are considered to produce novel as well as chemically and structurally diverse secondary metabolites. These metabolites are being used as clinical grade drug targets due to their less toxicity over other conventional drugs for diseases like cancer, microbial infections. Endophytes extracts are also exploited in food, agrichemical and biotechnology industries. Asparaginase of bacterial origin is widely used antitumor drug. The quint essential role of endophytes is their activity against microorganisms which can open gates in the field of biomedical research. This review mainly focuses on endophytes from medicinal plants as a source of antitumor and antimicrobial agents. Also highlights the need to focus on finding alternatives methods of endophytes isolation and production as well as characterization, purification and genetic transformations in order get maximum benefits.

scholarly journals Murine Cep290 phenotypes are modified by genetic backgrounds and provide an impetus for investigating disease modifier alleles

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 590 ◽  
Author(s):  
Simon A. Ramsbottom ◽  
Colin Miles ◽  
John A. Sayer
Keyword(s):  
Genetic Background ◽  
Primary Cilia ◽  
Joubert Syndrome ◽  
Biological Role ◽  
Murine Models ◽  
Disease Pathogenesis ◽  
Disease Modifier ◽  
Compare And Contrast ◽  
Broad Interest

The study of primary cilia is of broad interest both in terms of disease pathogenesis and the fundamental biological role of these structures. Murine models of ciliopathies provide valuable tools for the study of these diseases. However, it is important to consider the precise phenotype of murine models and how dependant it is upon genetic background. Here we compare and contrast murine models of Cep290, a frequent genetic cause of Joubert syndrome in order to refine our concept of genotype-phenotype correlations.

Essential role of Sharpin in TNFα dependent NFκB activation in primary hepatocytes

2012 ◽  
Vol 50 (01) ◽  
Author(s):  
N Lange ◽  
S Sieber ◽  
A Erhardt ◽  
G Sass ◽  
HJ Kreienkamp ◽  
...  
Keyword(s):  
Essential Role ◽  
Primary Hepatocytes

Different Abilities of Thrombin Receptor Activating Peptide and Thrombin to Induce Platelet Calcium Rise and Full Release Reaction

1995 ◽  
Vol 74 (05) ◽  
pp. 1323-1328 ◽  
Author(s):  
Dominique Lasne ◽  
José Donato ◽  
Hervé Falet ◽  
Francine Rendu
Keyword(s):  
Essential Role ◽  
Calcium Influx ◽  
Dense Granule ◽  
Receptor Interaction ◽  
Thrombin Receptor ◽  
Release Reaction ◽  
External Calcium ◽  
Maximum Rise ◽  
Granule Release

SummarySynthetic peptides (TRAP or Thrombin Receptor Activating Peptide) corresponding to at least the first five aminoacids of the new N-terminal tail generated after thrombin proteolysis of its receptor are effective to mimic thrombin. We have studied two different TRAPs (SFLLR, and SFLLRN) in their effectiveness to induce the different platelet responses in comparison with thrombin. Using Indo-1/AM- labelled platelets, the maximum rise in cytoplasmic ionized calcium was lower with TRAPs than with thrombin. At threshold concentrations allowing maximal aggregation (50 μM SFLLR, 5 μM SFLLRN and 1 nM thrombin) the TRAPs-induced release reaction was about the same level as with thrombin, except when external calcium was removed by addition of 1 mM EDTA. In these conditions, the dense granule release induced by TRAPs was reduced by over 60%, that of lysosome release by 75%, compared to only 15% of reduction in the presence of thrombin. Thus calcium influx was more important for TRAPs-induced release than for thrombin-induced release. At strong concentrations giving maximal aggregation and release in the absence of secondary mediators (by pretreatment with ADP scavengers plus aspirin), SFLLRN mobilized less calcium, with a fast return towards the basal level and induced smaller lysosome release than did thrombin. The results further demonstrate the essential role of external calcium in triggering sustained and full platelet responses, and emphasize the major difference between TRAP and thrombin in mobilizing [Ca2+]j. Thus, apart from the proteolysis of the seven transmembrane receptor, another thrombin binding site or thrombin receptor interaction is required to obtain full and complete responses.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

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