Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets

Sobieh, Basma H.; El‐Mesallamy, Hala O.; Kassem, Dina H.

doi:10.1016/j.heliyon.2023.e15700

Cited by 13 publications

(13 citation statements)

References 181 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It has been suggested that obesity’s impact on joints and its essence as a major factor in the development of OA lies in the union between increased weight and the ‘chronic micro-inflammatory state’ [ 38 ]. Weight overloading of joints in itself may cause an increase in the levels of IL-1β and TNFα and stimulate the degradation of cartilage ECM [ 39 ]. However, another key player is adipose tissue and its role as a potent source of cytokines, chemokines and other biologically active mediators, collectively known as adipokines [ 40 ].…”

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

“…However, another key player is adipose tissue and its role as a potent source of cytokines, chemokines and other biologically active mediators, collectively known as adipokines [ 40 ]. Some of these molecules maintain a chronic state of low-grade inflammation in obese individuals (such as TNFα, IL-1β, IL-6, adiponectin and leptin) and promote a catabolic state that degrades the joint, while others help preserve cartilage integrity [ 39 , 40 ]. In addition, the cellular composition of adipose tissue in thin and obese individuals varies.…”

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

“…Obesity is associated with a change in phenotype from M2 macrophages to classic M1-activated macrophages that release pro-inflammatory cytokines [ 41 ]. These complex mechanisms further involve other pathological conditions associated with obesity in the context of metabolic syndrome, such as dyslipidemia and insulin resistance [ 39 , 42 ].…”

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

“…Recent studies reported a link between the lipotoxicity present in dyslipidemia and the development of OA [ 43 , 44 ]. One of the aberrant responses seen in chondrocytes over the course of OA is the accumulation of intracellular lipids, the levels of which correlate with disease severity [ 39 ]. Furthermore, two enzymes important in lipid metabolism, namely cholesterol 25-hydroxylase and 25-hydroxycholesterol 7α-hydroxylase, were found to increase in OA states and were associated with a decrease in anabolic factors and the development of key OA features such as formation of osteophytes, synovitis and subchondral sclerosis.…”

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

“…Insulin resistance was also implicated in knee OA in the context of obesity and metabolic syndrome. Insulin has an important anabolic impact on articular cartilage by increasing the synthesis of collagen type II and proteoglycans, promoting chondrocyte proliferation and inhibiting the action of aggrecanases, TNFα and IL-1β [ 39 , 53 ]. Insulin resistance, therefore, likely makes the synovium and articular cartilage more susceptible to the pro-inflammatory activity of the above mediators.…”

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

See 4 more Smart Citations

Obesity-Related Knee Osteoarthritis—Current Concepts

Shumnalieva,

Kotov,

Monov

2023

Life

View full text Add to dashboard Cite

The knee is the joint most frequently involved in osteoarthritis and represents a significant contributor to patient morbidity and impaired functional status. Major risk factors include genetics, age, sex, mechanical load and obesity/metabolic syndrome. Recent studies highlighted the role of obesity and metabolic syndrome in the pathogenesis of knee osteoarthritis not simply through increased mechanical loading but the systemic effects of obesity-induced inflammation. The current concept of knee osteoarthritis is that of a ‘whole joint disease’, which highlights the involvement not only of articular cartilage but also the synovium, subchondral bone, ligaments and muscles. Obesity and metabolic syndrome are associated with higher levels of pro-inflammatory cytokines, increased production of adipokines with both protective and destructive effects on articular cartilage, an up-regulation of proteolytic enzymes such as matrix metalloproteinases and aggrecanases and an increase in free fatty acids and reactive oxygen species induced by dyslipidemia. These findings underscore that the adequate management of knee osteoarthritis needs to include an optimization of body weight and a beneficial mobility regimen. The possible introduction of pharmacological therapy targeting specific molecules involved in the pathogenesis of obesity-related osteoarthritis will likely also be considered in future therapeutic strategies, including personalized treatment approaches.

show abstract

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

Section: Obesity Metabolic Syndrome and Knee Oamentioning

confidence: 99%

See 3 more Smart Citations

Obesity-Related Knee Osteoarthritis—Current Concepts

Shumnalieva,

Kotov,

Monov

2023

Life

View full text Add to dashboard Cite

show abstract

Enhancement of Intracellular Cholesterol Efflux in Chondrocytes Leading to Alleviation of Osteoarthritis Progression

Lee,

Yang,

Kim

et al. 2024

Arthritis & Rheumatology

View full text Add to dashboard Cite

ObjectivesOsteoarthritis (OA) is the most common degenerative disease worldwide with no practical means of prevention and limited treatment options. Recently, our group unveiled a novel mechanism contributing to OA pathogenesis in association with abnormal cholesterol metabolism in chondrocytes. In this study, we aimed to establish a clinical link between lipid profiles and OA in humans, assess the effectiveness of cholesterol‐lowering drugs in suppressing OA development in mice, and uncover the cholesterol‐lowering mechanisms that effectively impede OA progression.MethodsFive clinically approved cholesterol‐lowering drugs (fenofibrate, atorvastatin, ezetimibe, niacin, and lomitapide) were injected into the knee joints or administered with diet to DMM‐induced OA mice fed a 2% high‐cholesterol diet. Gene expression linked to cholesterol metabolism were determined using microarray analysis. Furthermore, the in vivo functions of these genes were explored through intra‐articular injection of either its inhibitor or adenovirus.ResultsLogistic regression analysis confirmed a close relationship between the diagnostic criteria of hyperlipidemia based on serum lipid levels and OA incidence. Among the cholesterol‐lowering drugs examined, fenofibrate exerted the most significant protective effect against cartilage destruction, which was attributed to elevated levels of high‐density lipoprotein cholesterol that is crucial for cholesterol efflux. Notably, cholesterol efflux was suppressed during OA progression via downregulation of apolipoprotein A1 binding protein (AIBP) expression. Overexpression of AIBP effectively inhibits OA progression.ConclusionsOur results suggest that restoration of cholesterol homeostasis to a normal state through administration of fenofibrate or AIBP overexpression, both of which induce cholesterol efflux, offers an effective therapeutic option for OA.

show abstract

Proteomic and lipidomic landscape of the infrapatellar fat pad and its clinical significance in knee osteoarthritis

Tu,

Zhu,

et al. 2024

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

View full text Add to dashboard Cite

Beyond mechanical loading: The metabolic contribution of obesity in osteoarthritis unveils novel therapeutic targets

Cited by 13 publications

References 181 publications

Obesity-Related Knee Osteoarthritis—Current Concepts

Obesity-Related Knee Osteoarthritis—Current Concepts

Enhancement of Intracellular Cholesterol Efflux in Chondrocytes Leading to Alleviation of Osteoarthritis Progression

Proteomic and lipidomic landscape of the infrapatellar fat pad and its clinical significance in knee osteoarthritis

Contact Info

Product

Resources

About