The online version of this article (doi:10.1186/s13075-017-1473-z) contains supplementary material, which is available to authorized users.
Metabolic syndrome (MetS) may be associated with knee osteoarthritis (OA), but the association between the individual components and OA are not well-understood. We aimed to study the effect of hypercholesterolemia on synovial inflammation in knee OA.
OA was surgically induced in rabbits fed with standard diet (OA group, n = 10) or in rabbits fed with high fat diet (OA-HFD, n = 10). Healthy rabbits receiving standard diet (Control, n = 10) or fed with HFD (HFD, n = 6) were also monitored. Twelve weeks after OA induction, synovial membranes were isolated and processed for studies.
Animals fed HFD showed higher levels of total serum cholesterol, triglycerides and C-reactive protein than control rabbits. Twelve weeks after OA induction, synovial membrane inflammation and macrophage infiltration were increased in rabbits with OA, particularly in the OA-HFD group. Extensive decrease of synovial adipose tissue area, adipocyte size and perilipin-1A synthesis were observed in the OA-HFD group in comparison to the OA and control groups. The HFD further increased the proinflammatory mediators IL-1β, IL-6 and TNF in the OA synovium. However, the synovial gene expression of adipokines, such as leptin and adiponectin, were markedly decreased in the rabbits with OA, especially in the OA-HFD group, in correlation with adipose tissue loss. However, circulating leptin was upregulated in the HFD and OA-HFD groups.
Our results indicate that a HFD is an aggravating factor worsening synovial membrane inflammation during OA, guided by increased infiltration of macrophages and removal of the adipose tissue, together with a remarkable presence of proinflammatory factors. Synovial adipocytes and dyslipemia could probably play pivotal roles in OA joint deterioration in patients with MetS, supporting that the link between obesity and OA transcends mechanical loading.
Additional file 1: Figure S1. Synovial tissue collection. Photographs show the precise locations where the rabbit joint was accessed and the synovial membrane (SM) was collected. Half of the SM containing both stroma and lining was then fixed and embedded in paraffin for histological studies, and the other portion was immediately frozen and used for molecular biology studies. (TIF 376 kb)13075_2017_1473_MOESM1_ESM.tif
Alberti KG, Zimmet P, Shaw J, IDF Epidemiology Task Force Consensus Group. The metabolic syndrome–a new worldwide definition. Lancet (London, England). 2005;366:1059–62. CrossRef
Yoshimura N, Muraki S, Oka H, Tanaka S, Kawaguchi H, Nakamura K, et al. Accumulation of metabolic risk factors such as overweight, hypertension, dyslipidaemia, and impaired glucose tolerance raises the risk of occurrence and progression of knee osteoarthritis: a 3-year follow-up of the ROAD study. Osteoarthritis Cartilage. 2012;20:1217–26. CrossRefPubMed
Niu J, Clancy M, Aliabadi P, Vasan R, Felson DT. Metabolic syndrome, its components, and knee osteoarthritis: The Framingham Osteoarthritis Study. Arthritis Rheum. 2017;69:1194–203. CrossRef
de Munter W, Blom AB, Helsen MM, Walgreen B, van der Kraan PM, Joosten LA, et al. Cholesterol accumulation caused by low density lipoprotein receptor deficiency or a cholesterol-rich diet results in ectopic bone formation during experimental osteoarthritis. Arthritis Res Ther. 2013;15:R178. CrossRefPubMedPubMedCentral
De Munter W, Van der Kraan PM, Van den Berg WB, Van Lent PLEM. High systemic levels of low-density lipoprotein cholesterol: fuel to the flames in inflammatory osteoarthritis? Rheumatol (United Kingdom). 2016;55:16–24.
Martel E, Egner B, Brown SA, King JN, Laveissiere A, Champeroux P, et al. Comparison of high-definition oscillometry – a non-invasive technology for arterial blood pressure measurement – with a direct invasive method using radio-telemetry in awake healthy cats. J Feline Med Surg. 2013;15:1104–13. CrossRefPubMed
Harasymowicz NS, Clement ND, Azfer A, Burnett R, Salter DM, Simpson AHWR. Regional differences between perisynovial and infrapatellar adipose tissue depots and their response to class II and class III obesity in patients with osteoarthritis. Arthritis Rheum. 2017;69:1396–406. CrossRef
Roman-Blas JA, Mediero A, Tardío L, Portal-Nuñez S, Gratal P, Herrero-Beaumont G, et al. The combined therapy with chondroitin sulfate plus glucosamine sulfate or chondroitin sulfate plus glucosamine hydrochloride does not improve joint damage in an experimental model of knee osteoarthritis in rabbits. Eur J Pharmacol. 2017;794:8–14. CrossRefPubMed
Alvarez-Soria MA, Largo R, Santillana J, Sánchez-Pernaute O, Calvo E, Hernández M, et al. Long term NSAID treatment inhibits COX-2 synthesis in the knee synovial membrane of patients with osteoarthritis: differential proinflammatory cytokine profile between celecoxib and aceclofenac. Ann Rheum Dis. 2006;65:998–1005. CrossRefPubMedPubMedCentral
Ruifrok AC, Johnston DA. Quantification of histochemical staining by color deconvolution. Anal Quant Cytol Histol. 2001;23:291–9. PubMed
Largo R, Martínez-Calatrava MJ, Sánchez-Pernaute O, Marcos ME, Moreno-Rubio J, Aparicio C, et al. Effect of a high dose of glucosamine on systemic and tissue inflammation in an experimental model of atherosclerosis aggravated by chronic arthritis. Am J Physiol Heart Circ Physiol. 2009;297:H268–76. CrossRefPubMed
Blanchette-Mackie EJ, Dwyer NK, Barber T, Coxey RA, Takeda T, Rondinone CM, et al. Perilipin is located on the surface layer of intracellular lipid droplets in adipocytes. J Lipid Res. 1995;36:1211–26. PubMed
Oehler S, Neureiter D, Meyer-Scholten C, Aigner T. Subtyping of osteoarthritic synoviopathy. Clin Exp Rheumatol. 2002;20:633–40. PubMed
Giralt M, Domingo P, Guallar JP, Rodriguez de la Concepción ML, Alegre M, Domingo JC, et al. HIV-1 infection alters gene expression in adipose tissue, which contributes to HIV-1/HAART-associated lipodystrophy. Antivir Ther. 2006;11:729–40. PubMed
- Increased synovial lipodystrophy induced by high fat diet aggravates synovitis in experimental osteoarthritis
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II