High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis

Munter, W. de; Bosch, M.H. van den; Slöetjes, A.; Croce, Kevin; Vogl, Thomas; Roth, Johannes; Koenders, Marije I.; Loo, Fons A. J. van de; Berg, Wim B. van den; Kraan, P.M. van der; Lent, P.L.E.M. van

doi:10.1016/j.joca.2015.11.016

Cited by 59 publications

(54 citation statements)

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“…The inflammatory OA features showed deviant results, as ApoE*3Leiden.CETP females developed almost no osteophytes but demonstrated overall high synovitis scores independent of diet. These results contradict current literature in which excessive bone formation and synovitis due to high LDL cholesterol levels is described 51 . The gender differences may partly be explained by the significantly higher diet-induced plasma cholesterol levels observed in ApoE*3Leiden.CETP females, a discrepancy driven by sex hormones 52 .…”

Section: Discussioncontrasting

confidence: 99%

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Kozijn

Gierman

Ham

et al. 2018

Osteoarthritis and Cartilage

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Mouse model s u m m a r yObjective: Human cohort studies have demonstrated a role for systemic metabolic dysfunction in osteoarthritis (OA) pathogenesis in obese patients. To explore the mechanisms underlying this metabolic phenotype of OA, we examined cartilage degradation in the knees of mice from different genetic backgrounds in which a metabolic phenotype was established by various dietary approaches. Design: Wild-type C57BL/6J mice and genetically modified mice (hCRP, LDLr À/À . Leiden and ApoE*3-Leiden.CETP mice) based on C57BL/6J background were used to investigate the contribution of inflammation and altered lipoprotein handling on diet-induced cartilage degradation. High-caloric diets of different macronutrient composition (i.e., high-carbohydrate or high-fat) were given in regimens of varying duration to induce a metabolic phenotype with aggravated cartilage degradation relative to controls. Results: Metabolic phenotypes were confirmed in all studies as mice developed obesity, hypercholesteremia, glucose intolerance and/or insulin resistance. Aggravated cartilage degradation was only observed in two out of the twelve experimental setups, specifically in long-term studies in male hCRP and female ApoE*3Leiden.CETP mice. C57BL/6J and LDLr À/À . Leiden mice did not develop HFD-induced OA under the conditions studied. Osteophyte formation and synovitis scores showed variable results between studies, but also between strains and gender. Conclusions: Long-term feeding of high-caloric diets consistently induced a metabolic phenotype in various C57BL/6J (-based) mouse strains. In contrast, the induction of articular cartilage degradation proved variable, which suggests that an additional trigger might be necessary to accelerate diet-induced OA progression. Gender and genetic modifications that result in a humanized pro-inflammatory state (human CRP) or lipoprotein metabolism (human-E3L.CETP) were identified as important contributing factors. © 2017 Published by Elsevier Ltd on behalf of Osteoarthritis Research Society International. IntroductionOsteoarthritis (OA) is a progressive joint disease that is characterised by focal loss of articular cartilage, which impedes smooth joint movement and causes stiffness and pain. The most important risk factors for OA are age, gender and obesity. The latter being of specific interest in developed countries, where prolonged life expectancy and a progressive sedentary lifestyle in combination with a high caloric diet is predicted to exponentially increase the number of obese individuals and hence the prevalence of OA The association between knee OA and obesity has been comprehensively studied in humans. Weight loss was found to significantly reduce pain and increase mobility in knee OA patients 3 and reduced the risk of onset of the disease 4 . In obese adults, weight loss combined with exercise appears to be the most promising treatment and is therefore recommended by several international guidelines on the management of metabolic OA 5,6 .Moreover, overweight was found to ...

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Section: Discussioncontrasting

confidence: 99%

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Kozijn

Gierman

Ham

et al. 2018

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

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“…Furthermore, obesity and metabolic syndrome also suppress the production of HDL cholesterol, which exerts antiinflammatory effects on macrophages through down-regulation of TLR-induced proinflammatory cytokines. Mouse models of dietary and genetic-induced hypercholesterolemia increase knee OA pathology, even without increasing body weight (46)(47)(48)(49)(50). Moreover, statin treatment diminished OA severity in these models, supporting a direct role for cholesterol homeostasis in OA pathogenesis (for review, see ref.…”

Section: Perspectives On the Role Of Metabolic Inflammation In Oa Fromentioning

confidence: 89%

Review: Metabolic Regulation of Inflammation in Osteoarthritis

Bérenbaum

Griffin

Liu‐Bryan

2016

Arthritis & Rheumatology

185

167

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“…studied the effect of high systemic LDL cholesterol levels independent of weight in ApoE −/− mice. They found that the increased synovial inflammation and accelerated ectopic bone formation during experimental OA are derived from high LDL levels . Koskinen and colleauges found that elevated levels of LDL (by LDL‐receptor deficiency or a cholesterol‐rich diet), in an inflammatory OA model, induced pathology.…”

Section: Cholesterol: a New Risk Factor For Initiating Oamentioning

confidence: 99%

Cholesterol metabolism in pathogenesis of osteoarthritis disease

et al. 2017

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Several lines of research indicate that osteoarthritis (OA) is not only a joint disorder associated with mechanical stress and aging but also a 'metabolic syndrome' in which several risk factors work together to contribute to disease initiation and/or development. One such metabolic risk factor could be high cholesterol levels in the body. Even though high cholesterol level is a well-known risk factor for cardiovascular disorders, its possible role in musculoskeletal diseases, particularly OA, is not clear. The authors discuss the fundamental viewpoints on cholesterol involvement in the pathogenesis of OA, stressing the need for understanding the molecular mechanisms behind this association. This is the area of research needed to provide knowledge on how one should live to prevent OA development as well as to suggest new targets for drug therapy.

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High LDL levels lead to increased synovial inflammation and accelerated ectopic bone formation during experimental osteoarthritis

Abstract: Increased cholesterol levels strongly elevate synovial activation and ectopic bone formation in early-stage collagenase-induced OA.

Cited by 59 publications

References 45 publications

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Variable cartilage degradation in mice with diet-induced metabolic dysfunction: food for thought

Review: Metabolic Regulation of Inflammation in Osteoarthritis

Cholesterol metabolism in pathogenesis of osteoarthritis disease

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