Chronic inflammation during osteoarthritis is associated with an increased expression of CD161 during advanced stage

Sachdeva, M.P.; Aggarwal, Aditya; Sharma, Ravi; Randhawa, Arpan; Sahni, Daisy; Jacob, Justin; Sharma, Vinit; Aggarwal, Anjali

doi:10.1111/sji.12770

Cited by 17 publications

(15 citation statements)

References 36 publications

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“…Considering GAG as a direct product of MMP action on cartilage, the highest GAG in KL grade-II and III SFs was a clear indication of the maximum activity of MMPs at these grades [ 24 ]. Sachdeva et al [ 25 ] reported similar observation on the ethnically similar population as in the present study, wherein MMP-9 and MMP-13 were studied in SF of OA patients. The expression of both the MMPs was reported high in KL grade-II and KL grade-III SFs and subsides in KL grade-IV.…”

Section: Discussionsupporting

confidence: 84%

Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Ingale

Kulkarni

Electricwala³

et al. 2021

Genes

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Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1β, IL-15, PGE2 and NGF in early OA (Kellgren–Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1β and MMPs revealed expressional negative correlation.

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Section: Discussionsupporting

confidence: 84%

Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Ingale

Kulkarni

Electricwala³

et al. 2021

Genes

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“…Early studies reported that PAR2 expression was up-regulated by inflammatory mediators such as TNF-α, IL-1α and lipopolysaccharide (LPS) [22]. A growing body of evidences suggested that inflammation played a crucial role in OA pathogenesis [23]. Previous studies reported that PAR2-deficient mice exerted less cartilage degradation in experimental osteoarthritis [18,24].…”

Section: Discussionmentioning

confidence: 99%

Protease-activated receptor 2 (PAR-2) antagonist AZ3451 as a novel therapeutic agent for osteoarthritis

Huang

et al. 2019

Aging

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Osteoarthritis (OA) is a highly prevalent joint disorder blamed for pain and disability in older individuals. It's commonly accepted that inflammation, apoptosis, autophagy and cellular senescence participate in the progress of OA. Protease activated receptor 2 (PAR2), a member of the G-protein coupled receptors, is involved in the regulation of various inflammation diseases. Previous studies have identified PAR2 as a potential therapeutic target for the treatment of OA. Here, we investigated the role of PAR2 antagonist AZ3451 in inflammation response, apoptosis, autophagy and cellular senescence during OA. We confirmed that PAR2 expression was significantly upregulated in OA articular cartilage tissues as well as in interleukin 1β (IL-1β) stimulated chondrocytes. We demonstrated AZ3451 could prevent the IL-1β-induced inflammation response, cartilage degradation and premature senescence in chondrocytes. Further study showed that AZ3451 attenuated chondrocytes apoptosis by activating autophagy in vitro. The P38/MAPK, NF-κB and PI3K/AKT/mTOR pathways were involved in the protective effect of AZ3451. In vivo, we found that intra-articular injection of AZ3451 could ameliorate the surgery induced cartilage degradation in rat OA model. Our work provided a better understanding of the mechanism of PAR2 in OA, and indicated that PAR2 antagonist AZ3451 might serve as a promising strategy for OA treatment.

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“…During the course of OA, IL-1 produced by chondrocytes and synovial nucleated cells, activates MMP in cartilage, causing degradation of cartilage matrix [31]. Sachdeva et al reported that MMP-9 in SF and MMP-13 levels in serum and SF decreased in K-L grade 4 cases [32]. However, there is still need for studies evaluating biochemical biomarkers of different stages of GOA.…”

Section: Discussionmentioning

confidence: 99%

Level of Adiponectin, Leptin and Selected Matrix Metalloproteinases in Female Overweight Patients with Primary Gonarthrosis

Jarecki

Małecka‐Massalska

Polkowska

et al. 2021

JCM

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The aim of this study was to assess levels of adiponectin (ACRP-30) and leptin in serum and synovial fluid (SF) of overweight females with primary gonarthrosis (GOA) and to look for their correlations with clinical status and the level of biochemical OA biomarkers: matrix metalloproteinase (MMP) 1, MMP-9 and tissue inhibitor of metalloproteinase (TIMP-1). The studied group consisted of 39 overweight females undergoing primary total knee arthroplasty as a result of GOA. The stage of GOA was evaluated according to Knee Society Score (KSS), Ahlbäck and Kellgren–Lawrence (K-L) scores. Peripheral blood and SF were obtained. Levels of selected biomarkers were assessed using ELISA kits. The mean level of ACRP-30 in serum valued were 8393.80 ng/mL and in SF, 774.33 ng/mL, the mean concentration of leptin in serum was 32,040.74 pg/mL and in SF, 27,332.12 pg/mL. Levels of leptin in serum and SF correlated with body mass index (BMI), (p = 0.0005, and p = 0.0002, respectively). Levels of ACRP-30 in serum was correlated with clinical scores (Ahlbäck: p = 0.0214; K-L: p = 0.0146). ACRP-30 in SF correlated with ACRP-30 in serum (p = 0.0003), tended to negatively correlate with MMP-1 in serum (p = 0.0598) and positively correlate with pro-MMP-1 in SF (p = 0.0600). To conclude, this study confirms the correlations between concentrations of both, leptin and ACRP-30, comparing serum and SF. In overweight females, leptin levels increase with BMI and ACRP-30 serum level increase in more advanced GOA stages. Finally, leptin levels were correlated with TIMP-1 serum concentration, one of the biochemical markers of GOA.

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Chronic inflammation during osteoarthritis is associated with an increased expression of CD161 during advanced stage

Cited by 17 publications

References 36 publications

Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process

Protease-activated receptor 2 (PAR-2) antagonist AZ3451 as a novel therapeutic agent for osteoarthritis

Level of Adiponectin, Leptin and Selected Matrix Metalloproteinases in Female Overweight Patients with Primary Gonarthrosis

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