Degenerative joint disease induced by repeated intra-articular injections of monosodium urate crystals in rats as investigated by 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.

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

10.21203/rs.3.rs-758047/v1 ◽

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.

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

Bioengineering ◽

10.3390/bioengineering8110166 ◽

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.

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Phosphorus Concentration in Knee Joint Structures of Patients Following Replacement Surgery

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16040525 ◽

2019 ◽

Vol 16 (4) ◽

pp. 525 ◽

Cited By ~ 1

Author(s):

Ciosek Żaneta ◽

Kosik-Bogacka Danuta ◽

Łanocha-Arendarczyk Natalia ◽

Kot Karolina ◽

Karaczun Maciej ◽

...

Keyword(s):

Knee Joint ◽

Cruciate Ligament ◽

The Body ◽

Infrapatellar Fat Pad ◽

Emission Spectrometry ◽

Phosphorus Concentration ◽

Spongy Bone ◽

Fat Pad ◽

Hoffa’S Fat Pad ◽

P Concentration

The aim of the study was to assess phosphorus (P) concentration in structures of the knee joint—including the tibial spongy bone, articular cartilage, meniscus, anterior cruciate ligament, and infrapatellar fat pad (Hoffa’s fat pad)—of patients following knee joint replacement. The study also aimed to assess the influence of selected biological and environmental factors on P concentration in studied parts of the knee joint. Phosphorus concentration was determined using inductively coupled plasma-atomic emission spectrometry (ICP-AES). Statistically significant differences in P concentration were found between different elements of the knee joint. The highest P concentration was measured in the spongy bone (72,746.68 mg kg−1 dw) and the lowest in the Hoffa’s fat pad (1203.19 mg kg−1 dw). P levels were unaffected by gender, age, BMI, place of residence, smoking, or alcohol consumption. Data on P concentration in the osteoarticular elements of the knee may be useful in the interpretation and evaluation of biochemical, morphological, and mechanical changes occurring in the body.

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

Journal of Feline Medicine and Surgery ◽

10.1177/1098612x15606774 ◽

2016 ◽

Vol 19 (1) ◽

pp. 27-35 ◽

Cited By ~ 3

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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Induction of chondrogenesis and expression of superficial zone protein (SZP)/lubricin by mesenchymal progenitors in the infrapatellar fat pad of the knee joint treated with TGF-β1 and BMP-7

Biochemical and Biophysical Research Communications ◽

10.1016/j.bbrc.2008.08.138 ◽

2008 ◽

Vol 376 (1) ◽

pp. 148-153 ◽

Cited By ~ 55

Author(s):

Sang Yang Lee ◽

Toshiyuki Nakagawa ◽

A. Hari Reddi

Keyword(s):

Knee Joint ◽

Infrapatellar Fat Pad ◽

Fat Pad ◽

Superficial Zone ◽

Mesenchymal Progenitors ◽

Superficial Zone Protein ◽

Tgf Β1

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Factors Affecting the Aluminum, Arsenic, Cadmium and Lead Concentrations in the Knee Joint Structures

Frontiers in Public Health ◽

10.3389/fpubh.2021.758074 ◽

2021 ◽

Vol 9 ◽

Author(s):

Guoyong Li ◽

Chunfeng Xiong ◽

Wenhua Xu ◽

Runhong Mei ◽

Tao Cheng ◽

...

Keyword(s):

Knee Joint ◽

Cancellous Bone ◽

Toxic Elements ◽

Cruciate Ligament ◽

Toxic Element ◽

Infrapatellar Fat Pad ◽

Diabetic Patients ◽

Fat Pad ◽

Femoral Cartilage ◽

Anterior Cruciate

Background: Toxic elements, such as aluminum (Al), arsenic (As), cadmium (Cd), and lead (Pb), are persistent environmental pollutants that can cause adverse effects on the health of exposed individuals. Bone is one of the primary target organs of accumulation and potential damage from toxic elements.Objectives: This study was performed to determine the Al, As, Cd, and Pb concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus, tibial cartilage, tibial cancellous bone and infrapatellar fat pad. Furthermore, the aim of this study was to explore the relationships between toxic element concentrations and related factors such as gender, age, place of residence, hypertension and diabetes, and to determine the correlations among these toxic elements in knee joint structures.Methods: The samples used this study were collected from 51 patients following total knee arthroplasty. The Al, As, Cd, and Pb concentrations were determined using inductively coupled plasma optic emission spectrometry.Results: Significant differences were found in the Al, As, Cd, and Pb concentrations among the knee joint structures. Cd concentration in the tibial cancellous bone in women was significantly higher than in men. Pb concentration in the infrapatellar fat pad of urban patients was significantly higher as compared to rural patients. Al concentrations in the femoral cancellous bone, femoral cartilage, anterior cruciate ligament, meniscus and tibial cartilage were significantly higher in patients living in urban areas than in rural areas. As concentration in the tibial cancellous bone of diabetic patients was significantly higher compared to non-diabetic patients. In addition, significant Spearman's positive correlations were found between Al and Pb in the knee joint structures.Conclusion: The obtained results of the investigated toxic elements may serve as a basis for establishing the reference values of Al, As, Cd, and Pb in the knee joint structures. The results reported in the study provides novel data regarding the relationships between the toxic element concentrations and gender, age, place of residence, hypertension and diabetes in the studied structures of knee joint. Furthermore, new interactions among these toxic elements were noted.

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Relationship between the deep flexion of the knee joint and the dynamics of the infrapatellar fat pad after anterior cruciate ligament reconstruction via ultrasonography

Journal of Physical Therapy Science ◽

10.1589/jpts.31.569 ◽

2019 ◽

Vol 31 (7) ◽

pp. 569-572 ◽

Cited By ~ 1

Author(s):

Takashi Kitagawa ◽

Junsuke Nakase ◽

Yasushi Takata ◽

Kengo Shimozaki ◽

Kazuki Asai ◽

...

Keyword(s):

Anterior Cruciate Ligament ◽

Knee Joint ◽

Anterior Cruciate Ligament Reconstruction ◽

Ligament Reconstruction ◽

Cruciate Ligament ◽

Infrapatellar Fat Pad ◽

Fat Pad ◽

Cruciate Ligament Reconstruction ◽

Deep Flexion ◽

Anterior Cruciate

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Degenerative joint disease on MRI and physical activity: a clinical study of the knee joint in 320 patients

European Radiology ◽

10.1007/s003300050646 ◽

1999 ◽

Vol 9 (1) ◽

pp. 145-152 ◽

Cited By ~ 24

Author(s):

G. F. Bachmann ◽

E. Basad ◽

K. Rauber ◽

M. S. Damian ◽

W. S. Rau

Keyword(s):

Physical Activity ◽

Clinical Study ◽

Knee Joint ◽

Degenerative Joint Disease ◽

Joint Disease

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The Role of Fibrosis in Osteoarthritis Progression

Life ◽

10.3390/life11010003 ◽

2020 ◽

Vol 11 (1) ◽

pp. 3

Author(s):

Yeri Alice Rim ◽

Ji Hyeon Ju

Keyword(s):

Knee Joint ◽

Total Joint Replacement ◽

Cartilage Degeneration ◽

Critical Issue ◽

Degenerative Joint Disease ◽

Joint Disease ◽

Joint Movement ◽

Synovial Membrane Inflammation ◽

Osteoarthritis Progression

Osteoarthritis (OA) is a chronic degenerative joint disease where the main characteristics include cartilage degeneration and synovial membrane inflammation. These changes in the knee joint eventually dampen the function of the joint and restrict joint movement, which eventually leads to a stage where total joint replacement is the only treatment option. While much is still unknown about the pathogenesis and progression mechanism of OA, joint fibrosis can be a critical issue for better understanding this disease. Synovial fibrosis and the generation of fibrocartilage are the two main fibrosis-related characteristics that can be found in OA. However, these two processes remain mostly misunderstood. In this review, we focus on the fibrosis process in OA, especially in the cartilage and the synovium tissue, which are the main tissues involved in OA.

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