Pro-inflammatory cytokines: The link between obesity and osteoarthritis

Wang, Tian Tian; He, Chengqi

doi:10.1016/j.cytogfr.2018.10.002

Cited by 711 publications

(507 citation statements)

References 205 publications

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“…Based on accumulating evidence, OA is a low‐grade inflammatory disease and not simply attributed to wear and tear . The levels of various pro‐inflammatory cytokines are increased in OA tissues, including IL‐1β, IL‐6, TNF‐α, IL‐17 and IL‐18 . Among these pro‐inflammatory cytokines, increased IL‐1β levels have consistently been observed in the cartilage tissue, synovial fluid and the blood of patients with OA , and it plays a critical role in the pathogenesis of OA by inducing the chondrocyte anabolic and catabolic imbalance, including the downregulation of Collagen II and Aggrecan, as well as the upregulation of ADAMTS‐5 and MMP‐13 .…”

Section: Discussionmentioning

confidence: 99%

“…Based on accumulating evidence, OA is a low-grade inflammatory disease and not simply attributed to wear and tear [38]. The levels of various pro-inflammatory cytokines are increased in OA tissues, including IL-1b, IL-6, TNF-a, IL-17 and IL-18 [39][40][41]. Among these pro-inflammatory cytokines, increased IL-1b levels have consistently been observed in the cartilage tissue, synovial fluid and the blood of patients with OA [42][43][44], and it plays a critical role in Fig.…”

Section: Discussionmentioning

confidence: 99%

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Knockdown of SGK1 alleviates the IL‐1β‐induced chondrocyte anabolic and catabolic imbalance by activating FoxO1‐mediated autophagy in human chondrocytes

et al. 2019

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Osteoarthritis (OA) is a common joint disease characterized by the progressive degeneration of articular cartilage with no effective treatment methods available. Cartilage degeneration is closely related to an anabolic and catabolic imbalance in chondrocytes, and accumulating evidence has revealed that autophagy is a crucial protective mechanism that maintains the balance of anabolic and catabolic activities. Therefore, studies aiming to identify additional genes that regulate autophagy as a promising therapeutic strategy for OA are needed. In this study, we analyzed the http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE113825 datasets from Gene Expression Omnibus and validated that serum‐ and glucocorticoid‐regulated kinase 1 (SGK1) was upregulated in OA cartilage. Based on the results from loss‐of‐function studies, SGK1 silencing promoted the deposition of glycosaminoglycans in interleukin 1 beta (IL‐1β)‐treated chondrocytes, and significantly alleviated IL‐1β‐induced downregulation of Collagen II and Aggrecan, as well as the upregulation of a disintegrin and metalloproteinase with thrombospondin motifs 5 and matrix metalloproteinase‐13. Furthermore, SGK1 knockdown reversed the IL‐1β‐induced chondrocyte anabolic and catabolic imbalance by activating autophagy. Moreover, SGK1 directly bound to forkhead box protein O1 (FoxO1) and increased its phosphorylation, which in turn resulted in its translocation from the nucleus. The decreased FoxO1 levels led to a decrease in LC3‐I/LC3‐II conversion and Beclin‐1 levels, subsequently inhibiting autophagosome formation and increasing P62 levels, thus indicating a downregulation of autophagy. Taken together, we identified a critical role of SGK1 in the IL‐1β‐induced chondrocyte anabolic and catabolic imbalance, which may represent a potential novel therapeutic target for OA.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Knockdown of SGK1 alleviates the IL‐1β‐induced chondrocyte anabolic and catabolic imbalance by activating FoxO1‐mediated autophagy in human chondrocytes

et al. 2019

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“…Fourth, one of the major symptoms of BBS is obesity, which is believed to undermine the immune tolerance [34]. Obesity induces production of pro-inflammatory cytokines, such as TNF-α [35] and IL-6 [36], which might predispose the individual for the development of autoimmune diseases [37][38][39][40][41]. Thus, the BBSome might have an extrinsic role in the immune system via inducing obesity.…”

Section: Introductionmentioning

confidence: 99%

Altered hematopoietic system and self-tolerance in Bardet-Biedl Syndrome

Tsyklauri

Niederlová

Forsythe

et al. 2020

Preprint

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Bardet-Biedl Syndrome (BBS) is a pleiotropic genetic disease caused by dysfunction of primary cilia. The immune system of patients with BBS or another ciliopathy has not been investigated, most likely because hematopoietic cells do not form cilia. However, there are multiple indications that the impairment of the processes typically associated with cilia might influence the hematopoietic compartment and immunity. In this study, we analyzed clinical data of BBS patients as well as a corresponding mouse model of BBS4 deficiency. We uncovered that BBS patients have higher incidence of certain autoimmune diseases. BBS patients and animal models have elevated white blood cell levels and altered red blood cell and platelet compartments. Moreover, we observed that BBS4 deficiency alters the development and homeostasis of B cells in mice. Some of the hematopoietic system alterations were caused by the BBS-induced obesity.Overall, our study reveals a connection between a ciliopathy and the alterations of the immune system and the hematopoietic compartment.

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“…The basis for the multi-organ alterations seen in obesity remains unfolded (13), but the state of chronic, low-100 grade inflammation commonly associated to this condition is considered a major contributing factor (11). This is reflected by the increased concentrations of white adipose tissue-derived pro-inflammatory cytokines (TNF-α, IL-6, leptin) and the antiparallel decrease of antiinflammatory signals, as adiponectin, commonly observed in obesity (12,14,15). Additional hormonal perturbations, e.g., of gastro-intestinal factors, such as ghrelin and GLP-1 (16), as 105 well as the ectopic deposition of fat, mostly in the liver (i.e., steatosis), which defines a state of lipotoxicity (17), contribute also to the worsening of the metabolic profile of obese 6 patients.…”

Section: Introduction 75mentioning

confidence: 99%

Tetrahydrocannabinolic Acid a (THCA-A) Reduces Adiposity and Prevents Metabolic Disease Caused by Diet-Induced Obesity

Palomares

Ruíz-Pino

Garrido‐Rodríguez

et al. 2019

Preprint

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25Cannabis has remarkable therapeutic potential, but its clinical use is limited by the psychotropic activity of Δ 9 -tetrahydrocannabinol (Δ 9 -THC). Surprisingly, the biological profile of the non-narcotic native precursor of Δ 9 -THC (Δ 9 -THC acid A, Δ 9 -THCA-A) is still largely unexplored. We present evidence that Δ 9 -THCA-A is a partial and selective PPARγ modulator, endowed with lower adipogenic activity than the full PPARγ agonist rosiglitazone 30 (RGZ) and with an enhanced osteoblastogenic activity in human mesenchymal stem cells.Docking and in vitro functional assays indicated that Δ 9 -THCA-A binds to and activates PPARγ by acting at both the canonical and the alternative sites of the ligand-binding domain.Transcriptomic signatures at inguinal white adipose tissue (iWAT) from mice treated with Δ 9 -THCA-A confirmed its mode of action on PPARγ. Administration of Δ 9 -THCA-A in a mouse 35 model of high fat diet (HFD)-induced obesity significantly reduced fat mass and body weight gain, markedly ameliorating glucose intolerance and insulin resistance, and largely preventing liver steatosis, adipogenesis and macrophage infiltration in fat tissues. Additionally, immunohistochemistry, transcriptomic, and plasma biomarker analyses showed that treatment with Δ 9 -THCA-A caused browning of iWAT and displayed potent anti-inflammatory actions 40 in HFD mice. Altogether, our data validate the potential of Δ 9 -THCA-A as a low adipogenic PPARγ agonist, capable of substantially improving the symptoms of obesity-associated metabolic syndrome and inflammation. These findings suggest that Δ 9 -THCA-A, and perhaps non-decarboxylated Cannabis sativa extracts, are worth considering for addition to our inventory of cannabis medicines. 45Key words: Medicinal cannabis, Δ 9 -THCA-A, PPARγ, obesity, metabolic syndrome, inflammation 50 3 SIGNIFICANCE STATEMENTThe medicinal use of Cannabis is gaining momentum, despite the adverse psychotropic effects of Δ 9 -THC, the decarboxylation product of its naturally occurring and nonpsychotropic precursor Δ 9 -THCA-A. We present evidence that Δ 9 -THCA-A is a partial ligand agonist of PPARγ with lower adipogenic activity compared to the full PPARγ agonist 55 rosiglitazone (RGZ). Moreover, chronic administration of Δ 9 -THCA-A in a mouse model of high fat diet (HFD)-induced obesity significantly reduced body weight gain and fat mass, improved glucose intolerance and insulin resistance, and prevented liver steatosis and macrophage infiltration in fat tissues, additionally inducing white adipose tissue browning.Collectively, these observations qualify Δ 9 -THCA-A, a compound devoid of psychotropic 60 effects, as an efficacious pharmacological agent to manage metabolic syndrome and obesityassociated inflammation. 65Highlights -Δ 9 -THCA-A is a partial PPARγ ligand agonist with low adipogenic activity -Δ 9 -THCA-A enhances osteoblastogenesis in bone marrow derived mesenchymal stem cells.-Δ 9 -THCA-A reduces body weight gain, fat mass, and liver steatosis in HFD-fed mice 70 -Δ 9 -THCA-A impro...

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Pro-inflammatory cytokines: The link between obesity and osteoarthritis

Cited by 711 publications

References 205 publications

Knockdown of SGK1 alleviates the IL‐1β‐induced chondrocyte anabolic and catabolic imbalance by activating FoxO1‐mediated autophagy in human chondrocytes

Knockdown of SGK1 alleviates the IL‐1β‐induced chondrocyte anabolic and catabolic imbalance by activating FoxO1‐mediated autophagy in human chondrocytes

Altered hematopoietic system and self-tolerance in Bardet-Biedl Syndrome

Tetrahydrocannabinolic Acid a (THCA-A) Reduces Adiposity and Prevents Metabolic Disease Caused by Diet-Induced Obesity

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