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.

FGFR3 deficiency enhances CXCL12-dependent chemotaxis of macrophages via upregulating CXCR7 and aggravates joint destruction in mice

2019 ◽  
Vol 79 (1) ◽  
pp. 112-122 ◽  
Author(s):  
Liang Kuang ◽  
Jiangyi Wu ◽  
Nan Su ◽  
Huabing Qi ◽  
Hangang Chen ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Biological Effects ◽  
Joint Destruction ◽  
Myeloid Cells ◽  
Cartilage Destruction ◽  
Conditional Knockout ◽  
Synovial Joint ◽  
Macrophage Chemotaxis ◽  
Pathway Inhibition

ObjectivesThis study aims to investigate the role and mechanism of FGFR3 in macrophages and their biological effects on the pathology of arthritis.MethodsMice with conditional knockout of FGFR3 in myeloid cells (R3cKO) were generated. Gait behaviours of the mice were monitored at different ages. Spontaneous synovial joint destruction was evaluated by digital radiographic imaging and μCT analysis; changes of articular cartilage and synovitis were determined by histological analysis. The recruitment of macrophages in the synovium was examined by immunostaining and monocyte trafficking assay. RNA-seq analysis, Western blotting and chemotaxis experiment were performed on control and FGFR3-deficient macrophages. The peripheral blood from non-osteoarthritis (OA) donors and patients with OA were analysed. Mice were treated with neutralising antibody against CXCR7 to investigate the role of CXCR7 in arthritis.ResultsR3cKO mice but not control mice developed spontaneous cartilage destruction in multiple synovial joints at the age of 13 months. Moreover, the synovitis and macrophage accumulation were observed in the joints of 9-month-old R3cKO mice when the articular cartilage was not grossly destructed. FGFR3 deficiency in myeloid cells also aggravated joint destruction in DMM mouse model. Mechanically, FGFR3 deficiency promoted macrophage chemotaxis partly through activation of NF-κB/CXCR7 pathway. Inhibition of CXCR7 could significantly reverse FGFR3-deficiency-enhanced macrophage chemotaxis and the arthritic phenotype in R3cKO mice.ConclusionsOur study identifies the role of FGFR3 in synovial macrophage recruitment and synovitis, which provides a new insight into the pathological mechanisms of inflammation-related arthritis.

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 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 Home schooling through online teaching in the era of COVID-19: Exploring the role of home-related factors that deepen educational inequalities across European societies

2021 ◽  
pp. 147490412110233
Author(s):  
Kostas Dimopoulos ◽  
Christos Koutsampelas ◽  
Anna Tsatsaroni
Keyword(s):  
Technology Use ◽  
Online Teaching ◽  
Home Schooling ◽  
Information And Communications Technology ◽  
The European Union ◽  
Related Factors ◽  
School Conditions ◽  
Educational Environments ◽  
Teachers And Students

The COVID-19 pandemic has forced governments worldwide to produce solutions to the abruptly interrupted work in education. School systems appear to have responded rapidly, creating home schooling and online educational environments, where teachers and students would interact with safety. In this paper, we attempt a synthesis of Sen’s capability approach, Bourdieu’s theory of capital and Bernstein’s framework in order to theorize the relationships between home and school conditions and practices, and to analyse the data of the 2nd Survey of Schools: ICT in Education (a survey conducted in 2019 on behalf of the European Commission collecting data regarding digitalization in education and digital technologies in learning in the European Union). The survey is complemented by a second set of indicators provided by Eurostat to further investigate the availability and functionality of household space per family in selected European countries. We find significant differences in important social and environmental conversion factors, likely limiting children’s capability to benefit from digital schooling. The most important differences are found in regard to parents’ familiarity with information and communications technology use, while inequalities in environmental factors, such as overcrowded housing, are also existent. Overall, there are large inequalities within and between countries in Europe, which need to be addressed by policymakers.

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