scholarly journals Comparative Analysis of the Occurrence and Role of CX3CL1 (Fractalkine) and Its Receptor CX3CR1 in Hemophilic Arthropathy and Osteoarthritis

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Piotr Wojdasiewicz ◽  
Łukasz A. Poniatowski ◽  
Andrzej Kotela ◽  
Marta Skoda ◽  
Michał Pyzlak ◽  
...  

Objective. Hemophilic arthropathy is characterized by recurrent bleeding episodes in patients with hemophilia leading to irreversible joint degeneration. The involvement of CX3CL1 (fractalkine) and its receptor CX3CR1 was observed in the pathogenesis of numerous arthritis-associated diseases. Taking this into account, we have presented a study investigating the role of the CX3CL1/CX3XR1 axis in the course of hemophilic arthropathy, including the CX3CL1-dependent expression of CD56+, CD68+, and CD31+ cells along with evaluation of articular cartilage and synovial membrane morphology. Methods. The study was carried out using cases (n=20) of end-stage hemophilic arthropathy with a severe type of hemophilia A and control cases (n=20) diagnosed with osteoarthritis. The biofluids including blood serum and synovial fluid were obtained intraoperatively for the evaluation of CX3CL1 using the ELISA test. Tissue specimens including articular cartilage and synovial membrane were similarly collected during surgery and stained immunohistologically using selected antibodies including anti-CX3CR1, anti-CD56, anti-CD68, and anti-CD31. Additionally, the analysis included the assessment of articular cartilage, synovial membrane, and blood vessel morphology. Results. In our study, we have documented increased average concentration of CX3CL1 in the blood serum of the study group (7.16±0.53 ng/ml) compared to the control group (5.85±0.70 ng/ml) without statistically significant difference in synovial fluid concentration at the same time. We have observed an increased macrophage presence with more marked proliferation and fibrosis of the synovial membrane in the study group. Remaining results such as expression of CX3CR1 presence of NK cells and larger surface area of blood vessels within the synovial membrane were noted also without statistical significance. Conclusions. This study has demonstrated collective CX3CL1/CX3CR1 axis involvement in hemophilic arthropathy pathogenesis introducing new interesting diagnostics and a therapeutic target.

2018 ◽  
Vol 10 (2) ◽  
Author(s):  
Alexander Franz ◽  
Laura Joseph ◽  
Constantin Mayer ◽  
Jan-Frieder Harmsen ◽  
Holger Schrumpf ◽  
...  

Osteoarthritis (OA) is the most frequently diagnosed joint disorder worldwide with increasing prevalence and crucial impact on the quality of life of affected patients through chronic pain, decreasing mobility and invalidity. Although some risk factors, such as age, obesity and previous joint injury are well established, the exact pathogenesis of OA on a cellular and molecular level remains less understood. Today, the role of nitrosative and oxidative stress has not been investigated conclusively in the pathogenesis of OA yet. Therefore, the objective of this study was to identify biological substances for oxidative and nitrosative stress, which mirror the degenerative processes in an osteoarthritic joint. 69 patients suffering from a diagnosed knee pain participated in this study. Based on the orthopedic diagnosis, patients were classified into an osteoarthritis group (OAG, n=24) or in one of two control groups (meniscopathy, CG1, n=11; anterior cruciate ligament rupture, CG2, n=34). Independently from the study protocol, all patients underwent an invasive surgical intervention which was used to collect samples from the synovial membrane, synovial fluid and human serum. Synovial biopsies were analyzed histopathologically for synovitis (Krenn-Score) and immunohistochemically for detection of end products of oxidative (8-isoprostane F2α) and nitrosative (3-nitrotyrosine) stress. Additionally, the fluid samples were analyzed for 8-isoprostane F2α and 3-nitrotyrosine by competitive ELISA method. The analyzation of inflammation in synovial biopsies revealed a slight synovitis in all three investigated groups. Detectable concentrations of 3-nitrotyrosine were reported in all three investigated groups without showing any significant differences between the synovial biopsies, fluid or human serum. In contrast, significant increased concentrations of 8-isoprostane F2α were detected in OAG compared to both control groups. Furthermore, our data showed a significant correlation between the histopathological synovitis and oxidative stress in OAG (r=0.728, P<0.01). There were no significant differences between the concentrations of 8-isoprostane F2α in synovial fluid and human serum. The findings of the current study support the hypothesis that oxidative and nitrosative stress are components of the multi-factory pathophysiological formation of OA. It seems reasonable that an inflammatory process in the synovial membrane triggers the generation of oxidative and nitrosative acting substances which can lead to a further degradation of the articular cartilage. Based on correlations between the observed degree of inflammation and investigated biomarkers, especially 8-isoprostane F2α seems to be a novel candidate biomarker for OA. However, due to the finding that also both control groups showed increased concentrations of selected biomarkers, future studies have to validate the diagnostic potential of these biomarkers in OA and in related conditions of the knee joint.


2010 ◽  
Vol 67 (4) ◽  
pp. 286-290 ◽  
Author(s):  
Aleksandra Tomic-Lucic ◽  
Suzana Pantovic ◽  
Gvozden Rosic ◽  
Zdravko Obradovic ◽  
Mirko Rosic

Background/Aim. Many arguments prove the pathophysiologic role of histamine in the process of remodeling and joint destruction in rheumatoid arthritis. The aim of our study was to find out if there was a relation between histamine concentration in synovial fluid and blood with clinical expression of disease activity. Methods. Histamine concentration in synovial fluid and blood was determinated in 19 patients with rheumatoid arthritis. Histamine concentration measurement was based on the Shore's fluorometric method. Histamine index (HI) was evaluated as a ratio between histamine concentration in synovial fluid and blood. Disease activity score, DAS 28 (3), with three variables (erythrocyte sedimentation rate, the number of swelled joints and the number of tender joints) was also evaluated. Results. Our results showed that there was no significant difference in concentration of histamine in synovial fluid and blood related to disease activity. However, there was a significant difference in the histamine index which was increased proportionally with disease activity. Conclusion. Our study indicates that histamine index could be useful in estimation of rheumatoid arthritis activity.


2020 ◽  
pp. 1098612X2097779
Author(s):  
Siti M Zainal Ariffin ◽  
David Bennett ◽  
William R Ferrell ◽  
John C Lockhart ◽  
Lynette Dunning ◽  
...  

Objectives The aim of this study was to determine the presence of protease-activated receptor 2 (PAR2) and matriptase proteins and quantify PAR2 and matriptase mRNA expression in the articular cartilage and synovial membrane of cats with and without osteoarthritis (OA). Methods A total of 28 articular cartilage samples from adult cats (14 OA and 14 normal), 10 synovial membranes from adult cats (five OA and five normal) and three cartilage samples from 9-week-old fetal cats were used. The presence of PAR2 and matriptase in the cartilage and synovial membrane of the adult samples was detected by immunohistochemical (IHC) staining, while real-time PCR was used for mRNA expression analyses in all samples. Results PAR2 was detected in all OA and normal articular cartilage and synovial membrane samples but confined to only a few superficial chondrocytes in the normal samples. Matriptase was only detected in OA articular cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression were, however, detected in all cartilage and synovial membrane samples. PAR2 and matriptase mRNA expression levels in OA articular cartilage were five ( P <0.001) and 3.3 ( P <0.001) times higher than that of the healthy group, respectively. There was no significant difference ( P = 0.05) in the OA synovial membrane PAR2 and matriptase mRNA expression compared with the normal samples. Conclusions and relevance Detection of PAR2 and matriptase proteins and gene expression in feline articular tissues is a novel and important finding, and supports the hypothesis that serine proteases are involved in the pathogenesis of feline OA. The consistent presence of PAR2 and matriptase protein in the cytoplasm of OA chondrocytes suggests a possible involvement of proteases in cartilage degradation. Further investigations into the PAR2 and matriptase pathobiology could enhance our understanding of the proteolytic cascades in feline OA, which might lead to the development of novel therapeutic strategies.


2019 ◽  
Vol 4 (6) ◽  
pp. 221-229 ◽  
Author(s):  
Simon Donell

Subchondral bone remodelling is an integral part of osteoarthritis and involves the development of subchondral sclerosis seen on plain imaging, along with osteophyte formation. The development of these changes is due to persistent abnormal mechanical stresses which create a cellular and biomolecular response to microfractures in the subchondral bone and osteochondral junction. An early sign is bone marrow lesions seen on MRI scanning. Healing can occur at this stage by correcting the abnormal loads. Persistence leads to what is thought to be a delayed union or nonunion response by the bone. Microfractures of the osteochondral junction, coupled with articular cartilage fissuring and loss, allows synovial fluid to penetrate the subchondral bone along with cytokines and other molecules reacting with the bone cells to increase the pathological effects. This review gives an overview of the current thoughts on subchondral bone remodelling in osteoarthritis that is aimed at orthopaedic surgeons to help in the understanding of the pathogenesis of osteoarthritis and the role of surgical management. Cite this article: EFORT Open Rev 2019;4 DOI: 10.1302/2058-5241.4.180102


2020 ◽  
Vol 2020 ◽  
pp. 1-1
Author(s):  
Piotr Wojdasiewicz ◽  
Łukasz A. Poniatowski ◽  
Andrzej Kotela ◽  
Marta Skoda ◽  
Michał Pyzlak ◽  
...  


2012 ◽  
Vol 64 (9) ◽  
pp. 2917-2926 ◽  
Author(s):  
Jennifer M. Antonacci ◽  
Tannin A. Schmidt ◽  
Lisa A. Serventi ◽  
Matthew Z. Cai ◽  
YuYu L. Shu ◽  
...  

Tribologia ◽  
2018 ◽  
Vol 273 (3) ◽  
pp. 147-154
Author(s):  
Anna M. RYNIEWICZ ◽  
Andrzej RYNIEWICZ ◽  
Anna PUKALUK ◽  
Paweł PAŁKA

The aim of the conducted research was the evaluation of the topography and the structure of the superficial layer of meniscus and articular cartilage. These are surfaces that optimise the friction and lubrication process in the knee joint. The animal samples of the menisci and the articular cartilage were examined. The research was performed using scanning electron microscopes and an atomic force microscope. The structure of the surface of meniscus and articular cartilage is very regular. The collagenous fibres, which are embedded in the ground substance, are parallel to the surface. The undulation of the surface was observed. In the area of the anterior horn on tibia side of both menisci as well as in the anterior area of tibial plateau, the concavity and convexity pattern is evident. The observed cavities enable the accumulation of the synovial fluid. The synovial fluid plays the role of the lubricant in the knee joint, and its presence is highly desired during the load transmission.


Author(s):  
Jeffrey Kay ◽  
Muzammil Memon ◽  
Vito Z Zou ◽  
Andrew Duong ◽  
Nicole Simunovic ◽  
...  

ImportanceBiomarkers have promising potential to provide a cost-effective tool to identify patients with femoroacetabular impingement (FAI) who are most at risk and who may benefit most from early joint preservation surgery.ObjectiveTo assess the potential role of biomarkers in the diagnosis and prognosis of FAI.Evidence reviewThree databases (PubMed, Ovid (MEDLINE) and Embase) were searched on 20 August 2017 from database inception, and two reviewers independently and in duplicate screened the resulting literature. Methodological quality of all included papers was assessed using the Methodological Index for Non-Randomized Studies criteria. The results are presented in a narrative summary fashion using descriptive statistics including means, proportions and ranges.FindingsSeven studies (one retrospective laboratory series and six controlled laboratory studies) were identified including a total of 227 patients. The mean age of the patients was 41.6 years (range: 13–80), with a mean follow-up period of 29.9 months (SD=3.2). Markers of articular cartilage breakdown, including cartilage oligomeric matrix protein (COMP) and fibronectin–aggrecan complex (FAC), were identified in high concentrations in the serum and synovial fluid of patients with FAI, respectively. Moreover, mRNA expression of catabolic cytokines in the articular cartilage of patients with FAI has been reported.Conclusions and relevanceAlthough not yet used in clinical settings, several biomarkers of articular cartilage damage have been identified in the serum, synovial fluid and articular cartilage of patients with FAI. These findings provide promising insight into the potential role of biomarkers in guiding clinical practice and assisting with patient selection and preoperative counselling in patients with FAI and should be evaluated further.Level of evidenceIV, systematic review of level III and IV studies.


2020 ◽  
Author(s):  
Shaowei Wang ◽  
Mengbo Zhu ◽  
Yanjing Guo ◽  
Ruijia Yang ◽  
Yaqiong Chang ◽  
...  

Abstract Background: The study was performed to evaluate whether intra-articular injection of A2M has better effect than current commonly used Hyaluronic Acid (HA) injection therapy to attenuate cartilage degeneration in a rat anterior cruciate ligament transection (ACLT) osteoarthritis (OA) model.Method: In vivo effects of A2M and HA on cartilage degeneration were evaluated in rat surgery induced ACLT OA models. 100 rats were randomly divided into four groups: (a) Sham surgery + saline (Sham + S), (b) ACLT + A2M, (c) ACLT+HA, or (d) ACLT + saline (ACLT+S). The animals were sacrificed at 12 weeks after surgery. Histological staining was performed to assess cartilage damage. The concentration of MMP-13 and sGAG in synovial fluid lavages was measured using ELISA and spectrophotometric quantitative determination. OA-related gene expression was quantified by qPCR.Result: Indian ink staining showed that articular cartilage surface treated by A2M was relatively intact compared with the animals treated by ACLT with saline or HA injection. Histological staining indicated that early supplemental intra-articular injection of A2M attenuated OA pathogenesis in the rat ACLT model compared with the animals treated with saline and HA. However, supplemental intra-articular injection of HA showed no significant effect on cartilage protection for post traumatic OA compared with saline treatment. Elisa results showed A2M reduced the concentration of MMP-13 in synovial fluid compared with HA treatment group and other groups. RT-qPCR indicated that supplemental intra-articular A2M inhibits catabolism and enhances anabolic metabolism, while there was no significant difference in the expression of OA-related genes between ACLT+HA group and ACLT+S group. Conclusion: In rat model, intra-articular injection of A2M had obvious protective effects on cartilage degeneration compared with HA treatment. Major indexes of joint degeneration decreased, providing strong evidence for its intra-articular inhibitory effect. Meanwhile, we found no significant alleviation of articular cartilage pathogenesis in HA treated group, which suggests that the efficacy of HA is questionable and possibly transient, although it is extensively used to improve syndromes.


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