scholarly journals Degenerative Joint Disease Induced by Repeated Intra-Articular Injections of Monosodium Urate Crystals in Rats as Investigated by Translational Imaging

2021 ◽  
Author(s):  
Nathalie Accart ◽  
Janet Dawson ◽  
Michael Obrecht ◽  
Christian Lambert ◽  
Manuela Flueckiger ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Cyst Formation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Infrapatellar Fat Pad ◽  
Repeated Injection ◽  
Monosodium Urate ◽  
Fat Pad ◽  
Crystal Deposition ◽  
Msu Crystals

Abstract Effects of repeated injection of monosodium urate (MSU) crystals, in combination with lipopolysaccharide (LPS), into rat knee joints every two weeks for a maximum of five administrations were investigated. Joint swelling, nociception and hard/soft tissue changes were assessed longitudinally by non-invasive imaging. MSU crystals induced joint swelling, synovial membrane thickening, fibrosis of the infrapatellar fat pad, tidemark breaching, and cartilage invasion by inflammatory cells. Several inflammatory proteins were present in synovial fluid. A higher sensitivity to mechanical stimulus was detected in paws of limbs receiving MSU/LPS compared to saline-injected limbs. In MSU/LPS-challenged joints, magnetic resonance imaging (MRI) revealed increased synovial fluid volume in the posterior region of the joint, alterations in the infrapatellar fat pad reflecting a progressive decrease of fat volume and fibrosis formation, and a significant increase in the relaxation time T2 in femoral cartilage, consistent with a reduction of proteoglycan content. MRI also showed cyst formation in the tibia, femur remodeling, and T2 reductions in extensor muscles consistent with fibrosis development. Repeated intra-articular MSU/LPS injections in the rat knee joint induced pathology in multiple tissues and may be a useful means to investigate the relationship between urate crystal deposition and the development of degenerative joint disease.

scholarly journals Degenerative joint disease induced by repeated intra-articular injections of monosodium urate crystals in rats as investigated by translational imaging

2022 ◽  
Vol 12 (1) ◽  
Author(s):  
Nathalie Accart ◽  
Janet Dawson ◽  
Michael Obrecht ◽  
Christian Lambert ◽  
Manuela Flueckiger ◽  
...  
Keyword(s):  
Knee Joint ◽  
Inflammatory Cells ◽  
Cyst Formation ◽  
Degenerative Joint Disease ◽  
Joint Disease ◽  
Infrapatellar Fat Pad ◽  
Monosodium Urate ◽  
Fat Pad ◽  
Crystal Deposition ◽  
Translational Imaging

AbstractThe objective of this work was to assess the consequences of repeated intra-articular injection of monosodium urate (MSU) crystals with inflammasome priming by lipopolysaccharide (LPS) in order to simulate recurrent bouts of gout in rats. Translational imaging was applied to simultaneously detect and quantify injury in different areas of the knee joint. MSU/LPS induced joint swelling, synovial membrane thickening, fibrosis of the infrapatellar fat pad, tidemark breaching, and cartilage invasion by inflammatory cells. A higher sensitivity to mechanical stimulus was detected in paws of limbs receiving MSU/LPS compared to saline-injected limbs. In MSU/LPS-challenged joints, magnetic resonance imaging (MRI) revealed increased synovial fluid volume in the posterior region of the joint, alterations in the infrapatellar fat pad reflecting a progressive decrease of fat volume and fibrosis formation, and a significant increase in the relaxation time T2 in femoral cartilage, consistent with a reduction of proteoglycan content. MRI also showed cyst formation in the tibia, femur remodeling, and T2 reductions in extensor muscles consistent with fibrosis development. Repeated intra-articular MSU/LPS injections in the rat knee joint induced pathology in multiple tissues and may be a useful means to investigate the relationship between urate crystal deposition and the development of degenerative joint disease.

scholarly journals An Unusual Presentation of Gout Involving the Ankle Ligaments

2020 ◽  
Vol 20 (02) ◽  
pp. 80-85
Author(s):  
Tommy Tsang Cheung ◽  
Helen Ka Yan Chan ◽  
Gavin Ka Wing Lee
Keyword(s):  
Tendon Rupture ◽  
Imaging Techniques ◽  
Joint Disease ◽  
Monosodium Urate ◽  
Connective Tissues ◽  
Ankle Ligaments ◽  
Crystal Deposition ◽  
Non Invasive ◽  
Msu Crystals

Gout is the most common inflammatory arthritis due to deposition of monosodium urate (MSU) crystals in joints and connective tissues. In contrast to joint disease, the majority of extra-articular involvement remains asymptomatic in patients with gout. Achilles tendon is the most common site of involvement and the inflammation elicited by MSU crystals can be falsely attributed to injury or overuse. In addition, tendon or ligament damage secondary to MSU crystal deposition can lead to ligament tear or tendon rupture. However, the diagnosis of gout in patients with extra-articular involvement is often delayed or even missed because tissue sampling is not feasible in routine clinical practice. Advanced imaging techniques using ultrasound and dual-energy computer tomography (DECT) can detect MSU crystal deposition in a non-invasive manner and confirm the diagnosis of gout in patients with extra-articular involvement. The following case demonstrates an atypical presentation of gout causing multiple ligament tears in the ankle and highlights the role of DECT in the diagnosis of gout with extra-articular involvement.

scholarly journals THU0406 IDENTIFICATION OF INTRACELLULAR VACUOLES IN SYNOVIAL FLUID WITH CALCIUM PYROPHOSPHATE AND MONOSODIUM URATE CRYSTALS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 440.1-441
Author(s):  
M. L. Peral ◽  
I. Calabuig ◽  
A. Martín-Carratalá ◽  
M. Andrés ◽  
E. Pascual
Keyword(s):  
Clinical Practice ◽  
Synovial Fluid ◽  
Phase Contrast ◽  
Calcium Pyrophosphate ◽  
Monosodium Urate ◽  
Fluid Analysis ◽  
Cytoplasmic Vacuoles ◽  
Contrast Microscopy ◽  
Ordinary Light ◽  
Msu Crystals

Background:Synovial fluid analysis using polarized microscopy is the gold standard for the diagnosis of crystal-related arthritis. In our experience, we have noted that, when calcium pyrophosphate (CPP) crystals are observed, they sometimes appear within intracellular vacuoles. However, this phenomenon is not seen in those samples containing monosodium urate (MSU) crystals. This finding has been scantly reported in the literature, but may be useful in clinical practice to ensure accurate crystal identification.Objectives:Our study aims to assess whether the presence of vacuoles contributes to identifying the type of crystal, and also to gauge the frequency of their presentation.Methods:We conducted an observational study in a rheumatology unit between February and June of 2019. Synovial fluids containing CPP or MSU crystals, obtained in daily clinical practice, were consecutively included for analysis. Two observers simultaneously analyzed the presence of vacuoles by ordinary light and phase contrast microscopy in less than 24 hours after their extraction, using a microscope equipped with two viewing stations. The primary study variable was to determine whether CPP and MSU crystals are seen inside intracellular vacuoles, and to calculate the frequency of this finding for each type of crystal, estimating their 95% confidence interval (95% CI) and comparing rates using Fisher’s exact test.Results:Twenty-one samples were obtained. Data is given in the Table. MSU crystals were present in 7 (33.3%) and CPP crystals in 14 (66.6%). Interestingly, none of the MSU samples showed crystal-containing vacuoles (95% CI 0-35.4%). On the contrary, cytoplasmic vacuoles containing crystals were present in all of the CPP samples (95% CI 78.5-100%). The findings were confirmed by phase-contrast microscopy. Differences were statistically significant (p<0.001).Table.SAMPLES ACCORDING TO TYPE OF MICROCRYSTAL(n=21)SAMPLES WITH VACUOLS(UNDER ORDINARY LIGHT)SAMPLES WITH VACUOLS(UNDER PHASE CONTRAST)CPP (14; 66.6%)14 (100%)(95%CI 78.5-100%)14 (100%)(95%CI 78.5-100%)MSU (7; 33.3%)0 (0%)(95%CI 0-35.4%)0 (0%)(95%CI 0-35.4%)Conclusion:The presence of vacuoles may be a useful and easy way to differentiate MSU and CPP crystals when performing synovial fluid microscopy in clinical practice, since it appears to be a distinctive feature in CPP crystal fluids.References:[1]Kohn NN, Hughes RE, McCarty DJ Jr, Faires JS. The significance of calcium phosphate crystals in the synovial fluid of arthritic patients: the «pseudogout syndrome». II. Identification of crystals. Ann InternMed. 1962 May;56:738-45.[2]Pascual E, Sivera F, Andrés M. Synovial Fluid Analysis for Crystals. CurrOpRheumatol 2011;23:161-169.[3]McCarty DJ, Koopman WJ. Arthritis and allied conditions: A textbook of rheumatology, volumen 1. Lea &amp;Febiger. 1993.[4]Pascual E, Sivera F. Synovial fluid crystal Analysis. En Gout and other crystal arthropathies. Terkeltaub R ed. Elsevier; 2012: p.20-34.[5]Hwang HS, Yang CM, Park SJ, Kim HA. Monosodium Urate Crystal-Induced Chondrocyte Death via Autophagic Process. Int J Mol Sci. 2015 Dec 8;16(12):29265-77.Image 1. Microscopy with ordinary light. Cells with cytoplasmic vacuoles are observed, as well as abundant intra and extracellular CPP crystals.Image 2. Microscopy with phase contrast technique. Cells with intracellular vacuoles are observed inside which have microcrystals with parallelepiped morphology, compatible with CPP.Disclosure of Interests: :None declared

scholarly journals Single-Cell RNA-Sequencing Identifies Infrapatellar Fat Pad Macrophage Polarization in Acute Synovitis/Fat Pad Fibrosis and Cell Therapy

2021 ◽  
Vol 8 (11) ◽  
pp. 166
Author(s):  
Dimitrios Kouroupis ◽  
Thomas M. Best ◽  
Lee D. Kaplan ◽  
Diego Correa ◽  
Anthony J. Griswold
Keyword(s):  
Single Cell ◽  
Rna Sequencing ◽  
Transcriptional Profiling ◽  
Macrophage Polarization ◽  
Myeloid Cells ◽  
Cellular Heterogeneity ◽  
Joint Disease ◽  
Infrapatellar Fat Pad ◽  
Fat Pad ◽  
Single Cell Rna Sequencing

The pathogenesis and progression of knee inflammatory pathologies is modulated partly by residing macrophages in the infrapatellar fat pad (IFP), thus, macrophage polarization towards pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes is important in joint disease pathologies. Alteration of M1/M2 balance contributes to the initiation and progression of joint inflammation and can be potentially altered with mesenchymal stem cell (MSC) therapy. In an acute synovial/IFP inflammation rat model a single intra-articular injection of IFP-MSC was performed, having as controls (1) diseased rats not receiving IFP-MSC and (2) non-diseased rats. After 4 days, cell specific transcriptional profiling via single-cell RNA-sequencing was performed on isolated IFP tissue from each group. Eight transcriptomically distinct cell populations were identified within the IFP across all three treatment groups with a noted difference in the proportion of myeloid cells across the groups. Largely myeloid cells consisted of macrophages (>90%); one M1 sub-cluster highly expressing pro-inflammatory markers and two M2 sub-clusters with one of them expressing higher levels of canonical M2 markers. Notably, the diseased samples (11.9%) had the lowest proportion of cells expressing M2 markers relative to healthy (14.8%) and MSC treated (19.4%) samples. These results suggest a phenotypic polarization of IFP macrophages towards the pro-inflammatory M1 phenotype in an acute model of inflammation, which are alleviated by IFP-MSC therapy inducing a switch towards an alternate M2 status. Understanding the IFP cellular heterogeneity and associated transcriptional programs may offer insights into novel therapeutic strategies for disabling joint disease pathologies.

Persistence of Crystals in Stored Synovial Fluid Samples

2020 ◽  
Vol 47 (9) ◽  
pp. 1416-1423
Author(s):  
Sonia Pastor ◽  
José-Antonio Bernal ◽  
Rocío Caño ◽  
Silvia Gómez-Sabater ◽  
Fernando Borras ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Light Microscopy ◽  
Room Temperature ◽  
Polarized Light ◽  
Calcium Pyrophosphate ◽  
Polarized Light Microscopy ◽  
Tetraacetic Acid ◽  
Monosodium Urate ◽  
Prospective Longitudinal ◽  
Msu Crystals

Objective.Lack of access to polarized light microscopy is often cited as an argument to justify the clinical diagnosis of crystal-related arthritis. We assessed the influence of time since sampling and preservation methods on crystal identification in synovial fluid (SF) samples under polarized light microscopy.Methods.This was a prospective, longitudinal, observational factorial study, analyzing 30 SF samples: 12 with monosodium urate (MSU) crystals and 18 with calcium pyrophosphate (CPP) crystals. Each SF sample was divided into 4 subsamples (120 subsamples in total). Two were stored in each type of preserving agent, heparin or ethylenediamine tetraacetic acid (EDTA), at room temperature or at 4°C. Samples were analyzed the following day (T1), at 3 days (T2), and at 7 days (T3) by simple polarized light microscopy, and the presence of crystals was recorded.Results.The identification of crystals in the MSU group was similar between groups, with crystals observed in 11/12 (91.7%) room temperature samples and in 12/12 (100%) refrigerated samples at T3. Identification of CPP crystals tended to decrease in all conditions, especially when preserved with EDTA at room temperature [12/18 (66.7%) at T3], while less reduction was seen in refrigerated heparin-containing tubes.Conclusion.Preserving samples with heparin in refrigerated conditions allows delayed microscopic examination for crystals. Avoiding crystal-proven diagnosis because of the immediate unavailability of microscopy no longer appears justified.

Association of mineralisations in the stifle joint of domestic cats with degenerative joint disease and cranial cruciate ligament pathology

2016 ◽  
Vol 19 (1) ◽  
pp. 27-35 ◽  
Author(s):  
Katja Voss ◽  
Philemon Karli ◽  
Pierre M Montavon ◽  
Hans Geyer
Keyword(s):  
Medial Meniscus ◽  
Cruciate Ligament ◽  
Degenerative Joint Disease ◽  
Joint Capsule ◽  
Degenerative Changes ◽  
Joint Disease ◽  
Fat Pad ◽  
Cranial Cruciate Ligament ◽  
Stifle Joint ◽  
Periarticular Tissue

Objectives The aim of the study was to evaluate the prevalence, size, location and appearance of mineralisations in feline stifle joints, and to evaluate their relationship with osteoarthritis and cranial cruciate ligament (CrCL) status. Methods Presence or absence, and size of mineralisations were determined from lateral stifle radiographs of 25 cats with CrCL rupture, and 44 cat cadavers without CrCL rupture. Mineralisations were classified as small, medium or large. Prevalence was compared between the clinically affected cats and the cadavers; the cadaver group was subdivided into an age-matched and an older group. Ten stifles with varying sizes of mineralisations were prepared as whole-knee specimens for histopathology. Location and appearance of the mineralisations, and degenerative changes in the cruciate ligaments, menisci, articular cartilage and joint capsule are described. Results Prevalence of articular mineralisations was 0.76 in stifles of cats with CrCL rupture (mean ± SD age 8.6 ± 4.5 years), 0.64 in stifles of age-matched cat cadavers and 0.74 in older cat cadavers (mean ± SD age 17.0 ± 2.4 years). Cats with CrCL rupture had a higher percentage of medium and large mineralisations than cats without CrCL rupture. Microscopically, small mineralisations were calcifications usually located in the cranial horn of the medial meniscus. Larger mineralisations were found to be ossifications, commonly located in the joint capsule and fat pad. Cats with larger mineralisations showed more signs of osteoarthritis, including degenerative changes in the CrCL. Conclusions and relevance Mineralisations in feline stifle joints were found to differ in size, appearance and location. Small mineralisations were usually confined to the medial meniscus, as described previously; larger mineralisations tended to be located in the tissues cranial to the menisci and seemed to be associated with osteoarthritis and CrCL pathology. Large mineralisations in feline stifles are ossifications in periarticular tissue and are associated with degenerative joint disease.

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