An update on the association between metabolic syndrome and osteoarthritis and on the potential role of leptin in osteoarthritis

Gao, Yu-Hang; Zhao, Cheng-Wu; Liu, Bo; Dong, Ning; Ding, Lu; Li, Yeran; Liu, Jianguo; Wei, Feng; Qi, Xiaojun; Jin, Xueying

doi:10.1016/j.cyto.2020.155043

Cited by 41 publications

(30 citation statements)

References 125 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Proposed mechanisms include decreased proteoglycan synthesis, 28 degradation of cartilage matrix via IL-1 activated matrix metallopeptidases, 16 and leptin-induced chondrocyte apoptosis. 30 Thus, it is possible that increased serum levels of pro-inflammatory adipokines among overweight and obese individuals could at least partly explain our findings. However, as no inflammatory markers were related to the presently studied endpoints, we cannot draw any conclusions about such mechanisms from our results.…”

Section: Discussionmentioning

confidence: 87%

High body mass index is associated with increased risk for osteoarthritis of the first carpometacarpal joint during more than 30 years of follow-up

Rydberg¹,

Dahlin²,

Gottsäter

et al. 2020

RMD Open

View full text Add to dashboard Cite

IntroductionOsteoarthritis (OA) of the first carpometacarpal (CMC-1) joint is a common hand disorder with symptoms including pain and weakness of the thumb. Previous studies have associated high BMI with OA of weight-bearing joints, whereas studies regarding non-weight-bearing joints have shown conflicting results. Thus, the aim of this study was to investigate the influence of overweight and obesity on incident OA of the CMC-1 joint.MethodDuring 1974 to 1992, 33 346 participants aged 26–61 years were included in the population-based cohort Malmö Preventive Project. Endpoint data were retrieved from Swedish national registers until end of 2018. Sex-stratified Cox regression models adjusted for potential confounders were calculated using BMI as a continuous variable and stratified for normal weight, overweight and obesity.ResultsMedian follow-up was 36 years for men and 32 years for women. A one-unit increment of BMI was independently associated with incident OA of the CMC-1 joint in men (HR 1.12; 95% CI 1.09 to 1.15, p<0.001) and women (HR 1.05; 95% CI 1.03 to 1.08, p<0.001). Stratifying for BMI groups, obesity was independently associated with OA of the CMC-1 joint in men (HR 3.57; 95% CI 2.68 to 4.77, p<0.001) and women (HR 1.98; 95% CI 1.44 to 2.73, p<0.001).ConclusionHigh BMI and obesity are major risk factors for OA of the CMC-1 joint. The association was stronger among men but could be demonstrated also among women. Future studies are warranted to clarify underlying pathophysiological mechanisms for this association, enabling identification of potential therapeutic targets related to obesity in order to prevent the development of OA of the CMC-1 joint.

show abstract

Section: Discussionmentioning

confidence: 87%

High body mass index is associated with increased risk for osteoarthritis of the first carpometacarpal joint during more than 30 years of follow-up

Rydberg¹,

Dahlin²,

Gottsäter

et al. 2020

RMD Open

View full text Add to dashboard Cite

show abstract

“…Recent studies have reported that the level of leptin is not only elevated signi cantly in the human body with obesity but also increased in the serum and synovial uid collected from the patients with OA that is correlated with the severity of OA [48]. Hence, resent studies have suggested that the expressions of leptin and its receptor have been considered positively as a risk factor associated with the development of OA [49][50][51]. [52] IL-1 family, including IL-1α and IL-1β, is considered the most key cytokine associated with the pathogenesis of OA that induce the in ammatory catabolic process combined with other catabolic factors such as aging, obesity, and traumatic joint injury [53].…”

Section: Discussionmentioning

confidence: 99%

Acteoside counteracts interleukin-1β-induced catabolic processes through the modulation of mitogen-activated protein kinases and the NFκB cellular signaling pathway

Lim

Kim

et al. 2020

Preprint

View full text Add to dashboard Cite

Objectives To verify the anti-catabolic effects of acteoside [α-L-rhamnosyl-(1->3)-β-D-glucoside] against osteoarthritis and its anti-catabolic signaling pathway. Methods Primary rat chondrocytes were isolated enzymatically from the articular cartilage of rat knee joint. Cytotoxicity of acteoside was assessed by MTT and Cell Live/Dead assay. Proteoglycan content was measured by dimethylmethylene blue assay. The proteoglycan loss was assessed by histological analysis using safranin-O & fast green staining after ex vivo organ culture of articular cartilage. The alteration of catabolic factors such as cartilage degrading enzymes, pro-inflammation cytokines, and inflammatory mediators were assessed by qPCR, qRT-PCR, gelatin zymography, western blot, and cytokine array. Cellular signaling pathways were investigated by western blot and nucleus translocation. Acteoside was orally administrated to osteoarthritic animals generated by the destabilization of medial meniscus at the knee joint of mice for 8 weeks. Thereafter, proteoglycan loss was assessed by safranin-O & fast green staining. Results Acteoside did not decrease the viabilities of mouse fibroblast L929 cells used as a normal cells and primary rat chondrocytes. Acteoside counteracted the IL-1β-induced proteoglycan loss in the chondrocytes and articular cartilage through suppressing the expression and activation of cartilage-degrading enzyme such as matrix metalloproteinase (MMP)-13, MMP-1, and MMP-3. Furthermore, acteoside suppressed the expression of inflammatory mediators such as inducible nitric oxide synthase, cyclooxygenase-2, nitric oxide, and prostaglandin E2 in the primary rat chondrocytes treated with IL-1β. Subsequently, the expression of pro-inflammatory cytokines was decreased by acteoside in the primary rat chondrocytes treated with IL-1β. Moreover, acteoside suppressed not only the phosphorylation of mitogen-activated protein kinases in primary rat chondrocytes treated with IL-1β but also the translocation of NFκB from the cytosol to the nucleus through suppression of its phosphorylation. Oral administration of 5 and 10 mg/kg acteoside attenuated the progressive degeneration of articular cartilage in the osteoarthritic mouse model generated by destabilization of the medial meniscus. Conclusion Our findings indicate that acteoside is a promising potential anti-catabolic agent or supplement to attenuate or prevent progressive degeneration of articular cartilage.

show abstract

“…Recent studies have focused on identifying the relationship between MetS components and OA in order to understand its influence on the inflammatory process involved in the pathogenesis of the disease. An epidemiologic association between MetS and OA has been observed in clinical studies, especially with knee OA ( 38 ). Animal studies have also demonstrated that OA pathogenesis can be led by metabolic dysregulation ( 38 ).…”

Section: Metainflammation In Oamentioning

confidence: 96%

“…An epidemiologic association between MetS and OA has been observed in clinical studies, especially with knee OA ( 38 ). Animal studies have also demonstrated that OA pathogenesis can be led by metabolic dysregulation ( 38 ). Despite increasing evidence of an association between OA and MetS, the mechanisms linking these diseases are not fully understood ( 39 ).…”

Section: Metainflammation In Oamentioning

confidence: 96%

Purinergic System Signaling in Metainflammation-Associated Osteoarthritis

et al. 2020

View full text Add to dashboard Cite

Inflammation triggered by metabolic imbalance, also called metainflammation, is low-grade inflammation caused by the components involved in metabolic syndrome (MetS), including central obesity and impaired glucose tolerance. This phenomenon is mainly due to excess nutrients and energy, and it contributes to the pathogenesis of osteoarthritis (OA). OA is characterized by the progressive degeneration of articular cartilage, which suffers erosion and progressively becomes thinner. Purinergic signaling is involved in several physiological and pathological processes, such as cell proliferation in development and tissue regeneration, neurotransmission and inflammation. Adenosine and ATP receptors, and other members of the signaling pathway, such as AMP-activated protein kinase (AMPK), are involved in obesity, type 2 diabetes (T2D) and OA progression. In this review, we focus on purinergic regulation in osteoarthritic cartilage and how different components of MetS, such as obesity and T2D, modulate the purinergic system in OA. In that regard, we describe the critical role in this disease of receptors, such as adenosine A2A receptor (A2AR) and ATP P2X7 receptor. Finally, we also assess how nucleotides regulate the inflammasome in OA.

show abstract

An update on the association between metabolic syndrome and osteoarthritis and on the potential role of leptin in osteoarthritis

Cited by 41 publications

References 125 publications

High body mass index is associated with increased risk for osteoarthritis of the first carpometacarpal joint during more than 30 years of follow-up

High body mass index is associated with increased risk for osteoarthritis of the first carpometacarpal joint during more than 30 years of follow-up

Acteoside counteracts interleukin-1β-induced catabolic processes through the modulation of mitogen-activated protein kinases and the NFκB cellular signaling pathway

Purinergic System Signaling in Metainflammation-Associated Osteoarthritis

Contact Info

Product

Resources

About