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Modulation of the Inflammatory Process by Hypercholesterolemia in Osteoarthritis
- Source :
- Frontiers in Medicine, Frontiers in Medicine, Vol 7 (2020)
- Publication Year :
- 2020
- Publisher :
- Frontiers Media SA, 2020.
-
Abstract
- Objective: Several studies have linked metabolic syndrome to the development of osteoarthritis (OA) through hypercholesterolemia, one of its components. However, epidemiological studies showed contradictory results, and it is not clear how hypercholesterolemia itself, or oxidized LDL (oxLDL)-a pathological molecule potentially involved in this relationship-could be affecting OA. The objectives of this study were to investigate the effect of hypercholesterolemia induced by high-fat diet (HFD) in cartilage from OA rabbits, and how oxLDL affect human chondrocyte inflammatory and catabolic responses. Design: New Zealand rabbits were fed with HFD for 18 weeks. On week 6, OA was surgically induced. At the end of the study, cartilage damage and IL-1β, IL-6, MCP-1, MMP-13, and COX-2 expression in articular cartilage were evaluated. In addition, cultured human OA articular chondrocytes were treated with oxLDL at concentrations equivalent to those expected in synovial fluid from HFD rabbits, in the presence of IL-1β and TNFα. The effect of oxLDL on cell viability, nitric oxide production and catabolic and pro-inflammatory gene expression was evaluated. Results: HFD intake did not modify cartilage structure or pro-inflammatory and catabolic gene expression and protein presence, both in healthy and OA animals. OxLDL did not affect human chondrocyte viability, ADAMTS5 and liver X receptor (LXR) α gene expression, but decreased the induction of IL-1β, IL-6, MCP-1, MMP-13, iNOS, and COX-2 gene expression and MMP-13 and COX-2 protein presence, evoked by cytokines. Conclusions: Our data suggest that cholesterol intake per se may not be deleterious for articular cartilage. Instead, cholesterol de novo synthesis and altered cholesterol metabolism could be involved in the associations observed in human disease.
- Subjects :
- 0301 basic medicine
medicine.medical_specialty
Osteoarthritis
Chondrocyte
LDL
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Internal medicine
medicine
Synovial fluid
Viability assay
Liver X receptor
cartilage
Original Research
030203 arthritis & rheumatology
lcsh:R5-920
hypercholesterolemia
Cholesterol
business.industry
Cartilage
General Medicine
medicine.disease
osteoarthritis
030104 developmental biology
Endocrinology
medicine.anatomical_structure
chemistry
chondrocyte
Medicine
Tumor necrosis factor alpha
lipids (amino acids, peptides, and proteins)
business
lcsh:Medicine (General)
diet
Subjects
Details
- Language :
- English
- ISSN :
- 2296858X
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Frontiers in Medicine
- Accession number :
- edsair.doi.dedup.....44a5764ab55cbebfd6abf7ebb3074f66
- Full Text :
- https://doi.org/10.3389/fmed.2020.566250