Metabolic Syndrome Predisposes to Osteoarthritis: Lessons from Model System
Autor: | Sampath Samuel Joshua Pragasam, Vijayalakshmi Venkatesan |
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Rok vydání: | 2020 |
Předmět: |
medicine.medical_specialty
Knee Joint Biomedical Engineering Physical Therapy Sports Therapy and Rehabilitation Model system Osteoarthritis 03 medical and health sciences Chondrocytes 0302 clinical medicine Insulin resistance Internal medicine medicine Animals Immunology and Allergy Obesity Rats Wistar Clinical Research papers 030304 developmental biology Metabolic Syndrome 030203 arthritis & rheumatology 0303 health sciences business.industry Cartilage X-Ray Microtomography medicine.disease Rats medicine.anatomical_structure Endocrinology Subchondral bone Metabolic syndrome business Dyslipidemia |
Zdroj: | Cartilage |
ISSN: | 1947-6043 1947-6035 |
DOI: | 10.1177/1947603520980161 |
Popis: | Objective The present study aims to assess for temporal changes in tibial subchondral bone and cartilage in WNIN/Gr-Ob rats (portraying obesity, insulin resistance, dyslipidemia, impaired glucose tolerance, hypertension) in comparison with Wistar controls (WNIN) using anthropometry, micro-computed tomography (micro-CT), scanning electron microscopy (SEM), histopathology, enzyme-linked immunosorbent assay (ELISA), and immunofluorescence. Design Body weight, abdominal circumference, body mass index (BMI), lean/fat mass, serum tumor necrosis factor (TNF)-α levels were measured (ELISA), followed by ultrastructural analysis of tibial subchondral bone (micro-CT) and cartilage architecture (histopathology and SEM) in WNIN/Gr-Ob and WNIN rats with age (3, 6 and 9 months). Additionally, primary cultures of articular chondrocytes isolated from 6-month-old WNIN/Gr-Ob and WNIN rats were assessed for matrix metalloproteinase (MMP)-13 and Collagen type II (COL2A1) by immunofluorescence. Results WNIN/Gr-Ob rats exhibited frank obesity with increased BMI, lean and fat mass vis-à-vis significantly higher levels of serum TNF-α (6>9>3 months) as compared with the controls. With an increase in BMI, WNIN/Gr-Ob rats presented with tibial cartilage fibrillation, erosion, osteophyte formation (6 months) and subchondral bone cyst (9 months) confirmed by histology and SEM. An increase in subchondral trabecular bone volume (sclerosis with decreased plate porosity) was observed in all ages in WNIN/Gr-Ob rats compared to their Control. Gaining insights, primary cultures of articular chondrocytes complemented with altered cellular expressions of COL2A1 and MMP-13 from WNIN/Gr-Ob rats, indicating osteoarthritis (OA) progression. Conclusion Multiple metabolic perturbations featured in WNIN/Gr-Ob rats were effective to induce spontaneous OA-like degenerative changes affecting knee joints akin to human OA. |
Databáze: | OpenAIRE |
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