Potential Role of Hyaluronic Acid on Bone in Osteoarthritis: Matrix Metalloproteinases, Aggrecanases, and RANKL Expression are Partially Prevented by Hyaluronic Acid in Interleukin 1-stimulated Osteoblasts

2014 ◽  
Vol 41 (5) ◽  
pp. 945-954 ◽  
Author(s):  
Zvezdana Mladenovic ◽  
Anne-Sophie Saurel ◽  
Francis Berenbaum ◽  
Claire Jacques
Keyword(s):  
Hyaluronic Acid ◽  
Matrix Metalloproteinases ◽  
Potential Role ◽  
Proteolytic Enzymes ◽  
Interleukin 1 ◽  
Nuclear Factor Κb ◽  
Mrna Levels ◽  
Receptor Activator ◽  
Polymerase Chain

Objective.To determine the effect of hyaluronic acid (HA) on proteolytic enzymes and bone remodeling mediators induced by interleukin 1β (IL-1β) and related to cartilage catabolism in murine osteoblasts.Methods.Osteoblasts were obtained from Swiss mice and cultured for 3 weeks. HA-treated osteoblasts were incubated with 100 μg/ml HA during the last week of culture, then stimulated with IL-1β (10 ng/ml) for 24 h. The expression of matrix metalloproteinases 3 and 13 (MMP-3 and MMP-13), ADAMTS-4 and ADAMTS-5, tissue inhibitor of metalloproteinases (TIMP), osteoprotegerin, and receptor activator of nuclear factor-κB ligand (RANKL) was determined by real-time polymerase chain reaction. MMP-3 and MMP-13 release was assessed by Western blot analysis.Results.IL-1β increased the mRNA levels of MMP-3 and MMP-13 and ADAMTS-4 and ADAMTS-5 and release of MMP-3 and MMP-13. Seven days of HA treatment significantly prevented the IL-1β-increased mRNA levels of MMP-3 (−61%, p < 0.01), MMP-13 (−56%, p < 0.01), ADAMTS-4 (−58%, p < 0.05), ADAMTS-5 (−52%, p < 0.01), and RANKL (−49%, p < 0.05), but not TIMP. As well, IL-1β-induced production of MMP-3 and MMP-13 was inhibited, by 27% (p < 0.01) and 40% (p < 0.01), respectively.Conclusion.In an inflammatory context in murine osteoblasts, HA can inhibit the expression of MMP and ADAMTS. Because HA can counteract the production of these mediators in chondrocytes, its beneficial effect in osteoarthritis may be due to its action on cartilage and subchondral bone.

ILThe Infl uence of Resveratrol on the Synovial Expression of Matrix Metalloproteinases and Receptor Activator of NF-κB Ligand in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

2013 ◽  
Vol 68 (7-8) ◽  
pp. 336-342
Author(s):  
Mathias Glehr ◽  
Margherita Breisach ◽  
Sonja Walzer ◽  
Birgit Lohberger ◽  
Florentine Fürst ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Matrix Metalloproteinases ◽  
Nuclear Factor Κb ◽  
Qrt Pcr ◽  
Pharmacological Studies ◽  
Receptor Activator ◽  
Polymerase Chain ◽  
Fibroblast Like Synoviocytes

Medication of rheumatoid arthritis (RA) remains challenging and often controversial concerning side effects or long-term complications. We investigated the effect of resveratrol, a phytoalexin discussed for its chondro-protective and anti-inflammatory qualities, on the synovial expression of matrix-degrading enzymes like matrix metalloproteinases (MMPs) and bone-remodelling proteins in RA fibroblast-like synoviocytes (FLS). Interleukin-1β- stimulated RA-FLS were treated with 100 μM resveratrol for 24 h. To evaluate the effect of resveratrol on the amount of bound/combined MMPs, a Luminex® xMAP multiplexing technology was used. The alteration in expression of receptor activator of nuclear factor- κB ligand (RANKL) and osteoprotegrin (OPG) was measured by quantitative real-time polymerase chain reaction (qRT-PCR). Resveratrol reduced the expression of MMP-1 (p = 0.022), MMP-3 (p = 0.021), and MMP-9 (p = 0.047). qRT-PCR showed a significant reduction in the relative abundance of the transcripts of OPG (p = 0.012) and RANKL (p = 0.018). Our in vitro findings indicate that resveratrol could be a new target for further pharmacological studies in the field of RA. In the future it could play a role as a possible substitute or supplement to currently used drugs against RA to prevent cartilage matrix degradation and pathological bone resorption due to inhibition of MMPs and RANKL

scholarly journals Chest CT texture-based radiomics analysis in differentiating COVID-19 from other interstitial pneumonia

2021 ◽  
Author(s):  
Damiano Caruso ◽  
Francesco Pucciarelli ◽  
Marta Zerunian ◽  
Balaji Ganeshan ◽  
Domenico De Santis ◽  
...  
Keyword(s):  
Interstitial Pneumonia ◽  
Potential Role ◽  
Texture Features ◽  
Roc Curves ◽  
Chest Ct ◽  
Preliminary Evaluation ◽  
Rt Pcr ◽  
Mean Intensity ◽  
Polymerase Chain

Abstract Purpose To evaluate the potential role of texture-based radiomics analysis in differentiating Coronavirus Disease-19 (COVID-19) pneumonia from pneumonia of other etiology on Chest CT. Materials and methods One hundred and twenty consecutive patients admitted to Emergency Department, from March 8, 2020, to April 25, 2020, with suspicious of COVID-19 that underwent Chest CT, were retrospectively analyzed. All patients presented CT findings indicative for interstitial pneumonia. Sixty patients with positive COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) and 60 patients with negative COVID-19 RT-PCR were enrolled. CT texture analysis (CTTA) was manually performed using dedicated software by two radiologists in consensus and textural features on filtered and unfiltered images were extracted as follows: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPP), skewness, and kurtosis. Nonparametric Mann–Whitney test assessed CTTA ability to differentiate positive from negative COVID-19 patients. Diagnostic criteria were obtained from receiver operating characteristic (ROC) curves. Results Unfiltered CTTA showed lower values of mean intensity, MPP, and kurtosis in COVID-19 positive patients compared to negative patients (p = 0.041, 0.004, and 0.002, respectively). On filtered images, fine and medium texture scales were significant differentiators; fine texture scale being most significant where COVID-19 positive patients had lower SD (p = 0.004) and MPP (p = 0.004) compared to COVID-19 negative patients. A combination of the significant texture features could identify the patients with positive COVID-19 from negative COVID-19 with a sensitivity of 60% and specificity of 80% (p = 0.001). Conclusions Preliminary evaluation suggests potential role of CTTA in distinguishing COVID-19 pneumonia from other interstitial pneumonia on Chest CT.

scholarly journals Essential role of IRAK-4 protein and its kinase activity in Toll-like receptor–mediated immune responses but not in TCR signaling

2007 ◽  
Vol 204 (5) ◽  
pp. 1013-1024 ◽  
Author(s):  
Tatsukata Kawagoe ◽  
Shintaro Sato ◽  
Andreas Jung ◽  
Masahiro Yamamoto ◽  
Kosuke Matsui ◽  
...  
Keyword(s):  
Immune Responses ◽  
Kinase Activity ◽  
Interleukin 1 ◽  
Cell Receptor ◽  
Nuclear Factor Κb ◽  
Toll Like Receptor ◽  
Tcr Signaling ◽  
Mitogen Activated Protein

Interleukin-1 receptor–associated kinase 4 (IRAK-4) was reported to be essential for the Toll-like receptor (TLR)– and T cell receptor (TCR)–mediated signaling leading to the activation of nuclear factor κB (NF-κB). However, the importance of kinase activity of IRAK family members is unclear. In this study, we investigated the functional role of IRAK-4 activity in vivo by generating mice carrying a knockin mutation (KK213AA) that abrogates its kinase activity. IRAK-4KN/KN mice were highly resistant to TLR-induced shock response. The cytokine production in response to TLR ligands was severely impaired in IRAK-4KN/KN as well as IRAK-4−/− macrophages. The IRAK-4 activity was essential for the activation of signaling pathways leading to mitogen-activated protein kinases. TLR-induced IRAK-4/IRAK-1–dependent and –independent pathways were involved in early induction of NF-κB–regulated genes in response to TLR ligands such as tumor necrosis factor α and IκBζ. In contrast to a previous paper (Suzuki, N., S. Suzuki, D.G. Millar, M. Unno, H. Hara, T. Calzascia, S. Yamasaki, T. Yokosuka, N.J. Chen, A.R. Elford, et al. 2006. Science. 311:1927–1932), the TCR signaling was not impaired in IRAK-4−/− and IRAK-4KN/KN mice. Thus, the kinase activity of IRAK-4 is essential for the regulation of TLR-mediated innate immune responses.

Potential role of interleukin-1 in reproduction of a squamate reptile (Chalcides chalcides)

Placenta ◽  
1996 ◽  
Vol 17 (5-6) ◽  
pp. A48
Author(s):  
L. Paulesu ◽  
R. Romagnoli ◽  
G. Ghiarar
Keyword(s):  
Potential Role ◽  
Interleukin 1 ◽  
Squamate Reptile

Constitutive RNA synthesis for the yeast activator ADR1 and identification of the ADR1-5c mutation: implications in posttranslational control of ADR1

1986 ◽  
Vol 6 (11) ◽  
pp. 4026-4030
Author(s):  
C L Denis ◽  
C Gallo
Keyword(s):  
Rna Synthesis ◽  
Potential Role ◽  
Glucose Repression ◽  
Posttranslational Regulation ◽  
Mrna Levels ◽  
Recognition Sequence ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Kinase Phosphorylation

The regulation of mRNA production for the yeast positive activator ADR1, a gene required for the expression of the glucose-repressible alcohol dehydrogenase (ADH II), was studied. ADR1 mRNA levels did not vary when yeasts were switched from glucose- to ethanol-containing medium, while ADH II expression increased 100-fold. The mRNA for the ADR1-5c allele, which augments ADH II expression 60-fold during glucose repression, was not present in greater abundance than ADR1 mRNA. Additionally, the ccr1-1 allele, which blocks ADH2 mRNA formation and partially suppresses the ADR1-5c phenotype, did not alter the levels of ADR1 mRNA. These results indicate that ADR1 is not transcriptionally controlled. To determine the character of the ADR1-5c mutation, the region containing the mutation was identified and sequenced. At base pair +683 a G-to-A transition was detected in the ADR1 coding sequence which would result in the substitution of a lysine residue for an arginine at amino acid 228. The location of the ADR1-5c mutation in the interior of the ADR1 coding sequences suggests that it enhances the activity of an extant but inactive ADR1 protein rather than increases the abundance of ADR1 by altered translation of its mRNA. The ADR1-5c mutation occurs in a region of the polypeptide corresponding to a cyclic AMP-dependent protein kinase phosphorylation recognition sequence. The potential role of reversible phosphorylation in the posttranslational regulation of ADR1 is discussed.

The balance between p53 isoforms modulates the efficiency of HIV-1 infection in macrophages

2021 ◽  
Author(s):  
Yann Breton ◽  
Corinne Barat ◽  
Michel J. Tremblay
Keyword(s):  
Virus Replication ◽  
Potential Role ◽  
Host Factors ◽  
Fine Tuning ◽  
Mrna Levels ◽  
Cellular Environment ◽  
P53 Isoforms ◽  
Antiviral Role ◽  
Hiv 1

Several host factors influence HIV-1 infection and replication. The p53-mediated antiviral role in monocytes-derived macrophages (MDMs) was previously highlighted. Indeed, an increase in p53 level results in a stronger restriction against HIV-1 early replication steps through SAMHD1 activity. In this study, we investigated the potential role of some p53 isoforms in HIV-1 infection. Transfection of isoform-specific siRNA induces distinctive effects on the virus life cycle. For example, in contrast to a siRNA targeting all isoforms, a knockdown of Δ133p53 transcripts reduces virus replication in MDMs that is correlated with a decrease in phosphorylated inactive SAMHD1. Combination of Δ133p53 knockdown and Nutlin-3, a pharmacological inhibitor of MDM2 that stabilizes p53, further reduces susceptibility of MDMs to HIV-1 infection, thus suggesting an inhibitory role of Δ133p53 towards p53 antiviral activity. In contrast, p53β knockdown in MDMs increases the viral production independently of SAMHD1. Moreover, experiments with a Nef-deficient virus show that this viral protein plays a protective role against the antiviral environment mediated by p53. Finally, HIV-1 infection affects the expression pattern of p53 isoforms by increasing p53β and p53γ mRNA levels while stabilizing the protein level of p53α and some isoforms from the p53β subclass. The balance between the various p53 isoforms is therefore an important factor in the overall susceptibility of macrophages to HIV-1 infection, fine-tuning the p53 response against HIV-1. This study brings a new understanding of the complex role of p53 in virus replication processes in myeloid cells. Importance As of today, HIV-1 is still considered as a global pandemic without a functional cure, partly because of the presence of stable viral reservoirs. Macrophages constitute one of these cell reservoirs, contributing to the viral persistence. Studies investigating the host factors involved in cell susceptibility to HIV-1 infection might lead to a better understanding of the reservoir formation and will eventually allow the development of an efficient cure. Our team previously showed the antiviral role of p53 in macrophages, which acts by compromising the early steps of HIV-1 replication. In this study, we demonstrate the involvement of p53 isoforms, which regulates p53 activity and define the cellular environment influencing viral replication. In addition, the results concerning the potential role of p53 in antiviral innate immunity could be transposed to other fields of virology and suggest that knowledge in oncology can be applied to HIV-1 research.

scholarly journals Constitutive RNA synthesis for the yeast activator ADR1 and identification of the ADR1-5c mutation: implications in posttranslational control of ADR1.

1986 ◽  
Vol 6 (11) ◽  
pp. 4026-4030 ◽  
Author(s):  
C L Denis ◽  
C Gallo
Keyword(s):  
Rna Synthesis ◽  
Potential Role ◽  
Glucose Repression ◽  
Posttranslational Regulation ◽  
Mrna Levels ◽  
Recognition Sequence ◽  
Dependent Protein Kinase ◽  
Dependent Protein ◽  
Kinase Phosphorylation

The regulation of mRNA production for the yeast positive activator ADR1, a gene required for the expression of the glucose-repressible alcohol dehydrogenase (ADH II), was studied. ADR1 mRNA levels did not vary when yeasts were switched from glucose- to ethanol-containing medium, while ADH II expression increased 100-fold. The mRNA for the ADR1-5c allele, which augments ADH II expression 60-fold during glucose repression, was not present in greater abundance than ADR1 mRNA. Additionally, the ccr1-1 allele, which blocks ADH2 mRNA formation and partially suppresses the ADR1-5c phenotype, did not alter the levels of ADR1 mRNA. These results indicate that ADR1 is not transcriptionally controlled. To determine the character of the ADR1-5c mutation, the region containing the mutation was identified and sequenced. At base pair +683 a G-to-A transition was detected in the ADR1 coding sequence which would result in the substitution of a lysine residue for an arginine at amino acid 228. The location of the ADR1-5c mutation in the interior of the ADR1 coding sequences suggests that it enhances the activity of an extant but inactive ADR1 protein rather than increases the abundance of ADR1 by altered translation of its mRNA. The ADR1-5c mutation occurs in a region of the polypeptide corresponding to a cyclic AMP-dependent protein kinase phosphorylation recognition sequence. The potential role of reversible phosphorylation in the posttranslational regulation of ADR1 is discussed.

scholarly journals The Role of miR-21 in Osteoblasts–Osteoclasts Coupling In Vitro

Cells ◽  
2020 ◽  
Vol 9 (2) ◽  
pp. 479 ◽  
Author(s):  
Agnieszka Smieszek ◽  
Klaudia Marcinkowska ◽  
Ariadna Pielok ◽  
Mateusz Sikora ◽  
Lukas Valihrach ◽  
...  
Keyword(s):  
Cathepsin K ◽  
Nuclear Factor Κb ◽  
Tartrate Resistant Acid Phosphatase ◽  
Type I ◽  
Nuclear Factor ◽  
Paracrine Signaling ◽  
Receptor Activator ◽  
The Impact

MiR-21 is being gradually more and more recognized as a molecule regulating bone tissue homeostasis. However, its function is not fully understood due to the dual role of miR-21 on bone-forming and bone-resorbing cells. In this study, we investigated the impact of miR-21 inhibition on pre-osteoblastic cells differentiation and paracrine signaling towards pre-osteoclasts using indirect co-culture model of mouse pre-osteoblast (MC3T3) and pre-osteoclast (4B12) cell lines. The inhibition of miR-21 in MC3T3 cells (MC3T3inh21) modulated expression of genes encoding osteogenic markers including collagen type I (Coll-1), osteocalcin (Ocl), osteopontin (Opn), and runt-related transcription factor 2 (Runx-2). Inhibition of miR-21 in osteogenic cultures of MC3T3 also inflected the synthesis of OPN protein which is essential for proper mineralization of extracellular matrix (ECM) and anchoring osteoclasts to the bones. Furthermore, it was shown that in osteoblasts miR-21 regulates expression of factors that are vital for survival of pre-osteoclast, such as receptor activator of nuclear factor κB ligand (RANKL). The pre-osteoclast cultured with MC3T3inh21 cells was characterized by lowered expression of several markers associated with osteoclasts’ differentiation, foremost tartrate-resistant acid phosphatase (Trap) but also receptor activator of nuclear factor-κB ligand (Rank), cathepsin K (Ctsk), carbonic anhydrase II (CaII), and matrix metalloproteinase (Mmp-9). Collectively, our data indicate that the inhibition of miR-21 in MC3T3 cells impairs the differentiation and ECM mineralization as well as influences paracrine signaling leading to decreased viability of pre-osteoclasts.

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