Macroscale mesenchymal condensation to study cytokine-driven cellular and matrix-related changes during cartilage degradation

Background: Osteoarthritis (OA) is a degenerative disease of joint cartilage affecting the elderly people around the world. Visualization and quantification of cartilage is very much essential for the assessment of OA and rehabilitation of the affected people. Magnetic Resonance Imaging (MRI) is the most widely used imaging modality in the treatment of knee joint diseases. But there are many challenges in proper visualization and quantification of articular cartilage using MRI. Volume rendering and 3D visualization can provide an overview of anatomy and disease condition of knee joint. In this work, cartilage is segmented from knee joint MRI, visualized in 3D using Volume of Interest (VOI) approach. Methods: Visualization of cartilage helps in the assessment of cartilage degradation in diseased knee joints. Cartilage thickness and volume were quantified using image processing techniques in OA affected knee joints. Statistical analysis is carried out on processed data set consisting of 110 of knee joints which include male (56) and female (54) of normal (22) and different stages of OA (88). The differences in thickness and volume of cartilage were observed in cartilage in groups based on age, gender and BMI in normal and progressive OA knee joints. Results: The results show that size and volume of cartilage are found to be significantly low in OA as compared to normal knee joints. The cartilage thickness and volume is significantly low for people with age 50 years and above and Body Mass Index (BMI) equal and greater than 25. Cartilage volume correlates with the progression of the disease and can be used for the evaluation of the response to therapies. Conclusion: The developed methods can be used as helping tool in the assessment of cartilage degradation in OA affected knee joint patients and treatment planning.

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Bone morphogenetic protein 7 inhibits cartilage degradation in a rabbit model of osteoarthritis

Nature Clinical Practice Rheumatology ◽

10.1038/ncprheum0955 ◽

2009 ◽

Vol 5 (1) ◽

pp. 4-4 ◽

Cited By ~ 1

Keyword(s):

Bone Morphogenetic Protein ◽

Rabbit Model ◽

Cartilage Degradation ◽

Bone Morphogenetic Protein 7 ◽

Morphogenetic Protein

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Probiotics and Amelioration of Rheumatoid Arthritis: Significant Roles of Lactobacillus casei and Lactobacillus acidophilus

Microorganisms ◽

10.3390/microorganisms9051070 ◽

2021 ◽

Vol 9 (5) ◽

pp. 1070

Author(s):

Alok K. Paul ◽

Anita Paul ◽

Rownak Jahan ◽

Khoshnur Jannat ◽

Tohmina A. Bondhon ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Air Pollution ◽

Lactobacillus Acidophilus ◽

Lactobacillus Casei ◽

Autoimmune Disorder ◽

Cartilage Degradation ◽

Preclinical Studies ◽

Gastrointestinal Microbiota ◽

Specific Factors ◽

Lactobacillus Spp

Rheumatoid arthritis is a chronic autoimmune disorder that can lead to disability conditions with swollen joints, pain, stiffness, cartilage degradation, and osteoporosis. Genetic, epigenetic, sex-specific factors, smoking, air pollution, food, oral hygiene, periodontitis, Prevotella, and imbalance in the gastrointestinal microbiota are possible sources of the initiation or progression of rheumatoid arthritis, although the detailed mechanisms still need to be elucidated. Probiotics containing Lactobacillus spp. are commonly used as alleviating agents or food supplements to manage diarrhea, dysentery, develop immunity, and maintain general health. The mechanism of action of Lactobacillus spp. against rheumatoid arthritis is still not clearly known to date. In this narrative review, we recapitulate the findings of recent studies to understand the overall pathogenesis of rheumatoid arthritis and the roles of probiotics, particularly L. casei or L. acidophilus, in the management of rheumatoid arthritis in clinical and preclinical studies.

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

Genes ◽

10.3390/genes12070989 ◽

2021 ◽

Vol 12 (7) ◽

pp. 989

Author(s):

Dhanashri Ingale ◽

Priya Kulkarni ◽

Ali Electricwala ◽

Alpana Moghe ◽

Sara Kamyab ◽

...

Keyword(s):

Synovial Fluid ◽

Early Stage ◽

Challenge Test ◽

Degradation Process ◽

Cartilage Degradation ◽

Gene Expressions ◽

Inflammatory Microenvironment ◽

Protein Levels ◽

Advanced Stages ◽

Inflammatory Milieu

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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Emerging Natural-Product-Based Treatments for the Management of Osteoarthritis

Antioxidants ◽

10.3390/antiox10020265 ◽

2021 ◽

Vol 10 (2) ◽

pp. 265

Author(s):

Maria-Luisa Pérez-Lozano ◽

Annabelle Cesaro ◽

Marija Mazor ◽

Eric Esteve ◽

Sabine Berteina-Raboin ◽

...

Keyword(s):

Bone Resorption ◽

Natural Product ◽

Treatment Strategies ◽

Cartilage Degradation ◽

Therapeutic Strategies ◽

Clinical Models ◽

Osteoarthritic Joint ◽

Dietary Components ◽

New Treatment ◽

Review Current

Osteoarthritis (OA) is a complex degenerative disease in which joint homeostasis is disrupted, leading to synovial inflammation, cartilage degradation, subchondral bone remodeling, and resulting in pain and joint disability. Yet, the development of new treatment strategies to restore the equilibrium of the osteoarthritic joint remains a challenge. Numerous studies have revealed that dietary components and/or natural products have anti-inflammatory, antioxidant, anti-bone-resorption, and anabolic potential and have received much attention toward the development of new therapeutic strategies for OA treatment. In the present review, we provide an overview of current and emerging natural-product-based research treatments for OA management by drawing attention to experimental, pre-clinical, and clinical models. Herein, we review current and emerging natural-product-based research treatments for OA management.

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Exosomes derived from miR-126-3p-overexpressing synovial fibroblasts suppress chondrocyte inflammation and cartilage degradation in a rat model of osteoarthritis

Cell Death Discovery ◽

10.1038/s41420-021-00418-y ◽

2021 ◽

Vol 7 (1) ◽

Author(s):

Yan Zhou ◽

Jianghua Ming ◽

Yaming Li ◽

Bochun Li ◽

Ming Deng ◽

...

Keyword(s):

Synovial Fluid ◽

Apoptotic Cell ◽

Synovial Fibroblasts ◽

Cartilage Degeneration ◽

Cartilage Degradation ◽

Exosomal Mirnas ◽

Exosomal Mirna ◽

And Control ◽

And Cartilage

AbstractMicroRNAs (miRNAs) encapsulated within exosomes can serve as essential regulators of intercellular communication and represent promising biomarkers of several aging-associated disorders. However, the relationship between exosomal miRNAs and osteoarthritis (OA)-related chondrocytes and synovial fibroblasts (SFCs) remain to be clarified. Herein, we profiled synovial fluid-derived exosomal miRNAs and explored the effects of exosomal miRNAs derived from SFCs on chondrocyte inflammation, proliferation, and survival, and further assessed their impact on cartilage degeneration in a surgically-induced rat OA model. We identified 19 miRNAs within synovial fluid-derived exosomes that were differentially expressed when comparing OA and control patients. We then employed a microarray-based approach to confirm that exosomal miRNA-126-3p expression was significantly reduced in OA patient-derived synovial fluid exosomes. At a functional level, miRNA-126-3p mimic treatment was sufficient to promote rat chondrocyte migration and proliferation while also suppressing apoptosis and IL-1β, IL-6, and TNF-α expression. SFC-miRNA-126-3p-Exos were able to suppress apoptotic cell death and associated inflammation in chondrocytes. Our in vivo results revealed that rat SFC-derived exosomal miRNA-126-3p was sufficient to suppress the formation of osteophytes, prevent cartilage degeneration, and exert anti-apoptotic and anti-inflammatory effects on articular cartilage. Overall, our findings indicate that SFC exosome‐delivered miRNA-126-3p can constrain chondrocyte inflammation and cartilage degeneration. As such, SFC-miRNA-126-3p-Exos may be of therapeutic value for the treatment of patients suffering from OA.

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Synovial immunopathology in haemochromatosis arthropathy

Annals of the Rheumatic Diseases ◽

10.1136/ard.2009.120204 ◽

2009 ◽

Vol 69 (6) ◽

pp. 1214-1219 ◽

Cited By ~ 34

Author(s):

Gisela Ruiz Heiland ◽

Elmar Aigner ◽

Tomáš Dallos ◽

Enijad Sahinbegovic ◽

Veit Krenn ◽

...

Keyword(s):

Synovial Tissue ◽

Autosomal Recessive ◽

Mononuclear Cells ◽

Cartilage Degradation ◽

Grading System ◽

Synovial Hyperplasia ◽

Hereditary Haemochromatosis ◽

Low Degree ◽

Articular Damage ◽

Musculoskeletal Involvement

BackgroundHereditary haemochromatosis (HH) is a common autosomal recessive inherited disorder that frequently causes arthritis. The pathophysiology of musculoskeletal involvement is, however, unclear.ObjectiveTo analyse synovial tissue obtained at surgery from patients with HH arthropathy and compare it qualitatively and quantitatively with specimens from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).MethodsSynovial tissue from 15 patients with HH, 20 with RA and 39 with OA was obtained during surgery. A synovitis grading system was used to determine the severity of synovial inflammation. Using immunohistochemistry, synovial neovascularisation and infiltration of macrophages, neutrophils and lymphocytes were quantitatively assessed.ResultsSynovitis in HH arthropathy largely resembles OA with mild infiltration of mononuclear cells and lymphocytes, formation of synovial microvessels and a low degree of synovial hyperplasia. While many features of HH arthropathy are reminiscent of OA, macrophage and especially neutrophil invasion is clearly more prominent in HH arthropathy than in primary OA and mimics features of RA. This finding was observed particularly in synovial tissue of HH samples with marked haemosiderin deposition.DiscussionThe histological picture of the synovium in HH arthropathy largely resembles a process reminiscent of OA. Neutrophil invasion is, however, markedly increased in HH arthropathy, especially in joints with iron deposition. Accumulation of neutrophils may be crucial for the production of matrix enzymes, which enables cartilage degradation and more rapidly progressive articular damage.

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