High systemic levels of low-density lipoprotein cholesterol: fuel to the flames in inflammatory osteoarthritis?

Munter, W. de; Kraan, P.M. van der; Berg, Wim B. van den; Lent, P.L.E.M. van

doi:10.1093/rheumatology/kev270

Cited by 62 publications

(52 citation statements)

References 95 publications

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“…Again, this advocates a role for inflammation in OA development, as previously argued for the hCRP strain. For OA patients the benefit of statin therapy is unclear at present, as human studies investigating the effect of statins on OA development are scarce and a beneficial effect is not observed in all studies 55 . Potential beneficial effects might however be missed due to underdosing, as we have previously shown that the optimal lipid-lowering statin dose is much lower than the threshold for the anti-inflammatory effects 56 .…”

Section: Discussionmentioning

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: Discussionmentioning

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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“…Additionally, cholesterol accumulation in the cartilage can impair the efflux function of cartilage, hence inducing OA [27, 28]. Oxidized LDL can activate synovial cells such as macrophages, endothelial cells, and synovial fibroblasts, resulting in release of growth factors, MMP, and proinflammatory cytokines, causing cartilage destruction and bone deformations [29]. …”

Section: Discussionmentioning

confidence: 99%

Metabolic Syndrome Increases the Risk for Knee Osteoarthritis: A Meta‐Analysis

Wang

Cheng

Shao

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Background. Studies revealed that metabolic factors might contribute substantially to osteoarthritis (OA) pathogenesis. There has been an increasing interest to understand the relationship between knee OA and the metabolic syndrome (MetS). The purpose of this study was to explore the association between metabolic syndrome and knee osteoarthritis using meta-analysis. Methods. Databases, including PUBMED, EMBASE, and the Cochrane Library, were searched to get relevant studies. Data were extracted separately by two authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Results. The meta-analysis was finished with 8 studies with a total of 3202 cases and 20968 controls finally retrieved from the database search. The crude pooled OR is 2.24 (95% CI = 1.38–3.64). Although there was significant heterogeneity among these studies, which was largely accounted for by a single study, the increase in risk was still significant after exclusion of that study. The pooled adjusted OR remained significant with pooled adjusted OR 1.05 (95% CI = 1.03–1.07, p < 0.00001). No publication bias was found in the present meta-analysis. Conclusions. The synthesis of available evidence supports that metabolic syndrome increases the risk for knee osteoarthritis, even after adjustment for many risk factors.

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“…There is emerging evidence suggesting that dyslipidemia, and particularly high oxidized LDL-cholesterol, has a role in osteoarthritis pathology independent of obesity and mechanical overload 74–77 . The hip, knee and hand joints may have different susceptibility to metabolic and non-metabolic factors 78,79 .…”

Section: Comorbiditiesmentioning

confidence: 99%

Clinical Factors, Disease Parameters, and Molecular Therapies Affecting Osseointegration of Orthopedic Implants

et al. 2016

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Total hip and knee arthroplasty are effective interventions for management of end-stage arthritis. Indeed, about 7 million Americans are currently living with artificial hip and knee joints. The majority of these individuals, however, will outlive their implants and require revision surgeries, mostly due to poor implant osseointegration and aseptic loosening. Revisions are potentially avoidable with better management of patient-related risk factors that affect the osseointegration of orthopedic implants. In this review, we summarize the published clinical literature on the role of demographics, biologic factors, comorbidities, medications and aseptic loosening risk. We focus on several systemic and local factors that are particularly relevant to implant osseointegration. Examples include physiological and molecular processes that are linked to hyperglycemia, oxidative stress, metabolic syndrome and dyslipidemia. We discuss how orthopedic implant osseointegration can be affected by a number of molecular therapies that are antiresorptive or bone anabolic (i.e. calcium, vitamin D, bisphosphonates, calcitonin, strontium, hormone replacement therapy, selective estrogen-receptor modulators).

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High systemic levels of low-density lipoprotein cholesterol: fuel to the flames in inflammatory osteoarthritis?

Cited by 62 publications

References 95 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

Metabolic Syndrome Increases the Risk for Knee Osteoarthritis: A Meta‐Analysis

Clinical Factors, Disease Parameters, and Molecular Therapies Affecting Osseointegration of Orthopedic Implants

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