Leukotriene D4 induces cellular senescence in osteoblasts

Wei, Jinsong; Chen, Siyuan; Guo, Weixiong; Feng, Bailin; Yang, Shukai; Huang, Chengshuo; Chu, Jiaqi

doi:10.1016/j.intimp.2017.12.027

Cited by 10 publications

(4 citation statements)

References 31 publications

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“…Moreover, the levels of cyclooxygenase and its major product, prostaglandin E2 (PGE2), are increased in both replicative and premature senescence ( 17 ). Leukotriene D4 plays a role in cellular senescence ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Senescence-associated secretory phenotype and its impact on oral immune homeostasis

et al. 2022

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The senescence-associated secretory phenotype (SASP), which accumulates over the course of normal aging and in age-related diseases, is a crucial driver of chronic inflammation and aging phenotypes. It is also responsible for the pathogenesis of multiple oral diseases. However, the pathogenic mechanism underlying SASP has not yet been fully elucidated. Here, relevant articles on SASP published over the last five years (2017–2022) were retrieved and used for bibliometric analysis, for the first time, to examine SASP composition. More than half of the relevant articles focus on various cytokines (27.5%), growth factors (20.9%), and proteases (20.9%). In addition, lipid metabolites (13.1%) and extracellular vesicles (6.5%) have received increasing attention over the past five years, and have been recognized as novel SASP categories. Based on this, we summarize the evidences demonstrating that SASP plays a pleiotropic role in oral immunity and propose a four-step hypothetical framework for the progression of SASP-related oral pathology—1) oral SASP development, 2) SASP-related oral pathological alterations, 3) pathological changes leading to oral immune homeostasis disruption, and 4) SASP-mediated immune dysregulation escalating oral disease. By targeting specific SASP factors, potential therapies can be developed to treat oral and age-related diseases.

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Section: Discussionmentioning

confidence: 99%

Senescence-associated secretory phenotype and its impact on oral immune homeostasis

et al. 2022

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“…Leukotriene d4 methyl ester was higher in the Old group and was also significantly positively correlated within the Old group as identified by the WGCNA. Leukotriene d4 methyl ester can cause increased vascular permeability and vasodilatation, playing a vital role in allergic and inflammatory processes ( 81 ). The elevation of both metabolites suggests that the old giant pandas were experiencing inflammation.…”

Section: Discussionmentioning

confidence: 99%

Age-related alterations in metabolome and microbiome provide insights in dietary transition in giant pandas

Liu,

Li,

Zhong

et al. 2023

mSystems

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We conducted UPLC-MS-based metabolomics, 16S rRNA, and metagenome sequencing on the fecal samples of 44 captive giant pandas ( Ailuropoda melanoleuca ) from four age groups (i.e., Cub, Young, Adult, and Old) to comprehensively understand age-related changes in the metabolism and gut microbiota of giant pandas. We characterized the metabolite profiles of giant pandas based on 1,376 identified metabolites, with 152 significantly differential metabolites (SDMs) found across the age groups. We found that the metabolites and the composition/function of the gut microbiota changed in response to the transition from a milk-dominant diet in panda cubs to a bamboo-specific diet in young and adult pandas. Lipid metabolites such as choline and hippuric acid were enriched in the Cub group, and many plant secondary metabolites were significantly higher in the Young and Adult groups, while oxidative stress and inflammatory related metabolites were only found in the Old group. However, there was a decrease in the α-diversity of gut microbiota in adult and old pandas, who exclusively consume bamboo. The abundance of bacteria related to the digestion of cellulose-rich food, such as Firmicutes, Streptococcus, and Clostridium, significantly increased from the Cub to the Adult group, while the abundance of beneficial bacteria such as Faecalibacterium , Sarcina, and Blautia significantly decreased. Notably, several potential pathogenic bacteria had relatively high abundances, especially in the Young group. Metagenomic analysis identified 277 CAZyme genes including cellulose degrading genes, and seven of the CAZymes had abundances that significantly differed between age groups. We also identified 237 antibiotic resistance genes (ARGs) whose number and diversity increased with age. We also found a significant positive correlation between the abundance of bile acids and gut bacteria, especially Lactobacillus and Bifidobacterium . Our results from metabolome, 16S rRNA, and metagenome data highlight the important role of the gut microbiota-bile acid axis in the regulation of age-related metabolism and provide new insights into the lipid metabolism of giant pandas. IMPORTANCE The giant panda is a member of the order Carnivora but is entirely herbivorous. The giant panda’s specialized diet and related metabolic mechanisms have not been fully understood. It is therefore crucial to investigate the dynamic changes in metabolites as giant pandas grow and physiologically adapt to their herbivorous diet. This study conducted UPLC-MS-based metabolomics 16S rRNA, and metagenome sequencing on the fecal samples of captive giant pandas from four age groups. We found that metabolites and the composition/function of gut microbiota changed in response to the transition from a milk-dominant diet in cubs to a bamboo-specific diet in young and adult pandas. The metabolome, 16S rRNA, and metagenome results highlight that the gut microbiota-bile acid axis has an important role in the regulation of age-related metabolism, and our study provides new insights into the lipid metabolism of giant pandas.

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“…LTB‐4 promotes peripheral blood mononuclear cell differentiation into osteoclasts in a RANKL‐dependent manner, 38 and it reduces mineralized nodule formation and alkaline phophatase (ALP) activity in primary osteoblasts 39 . LTD‐4, another leukotriene metabolite, significantly increases the expression of p53, p21, and plasminogen activator inhibitor‐1 (PAI‐1), as well as the activity of senescence‐associated β‐galactosidase (SA‐β‐Gal), with commensurate reduction in SIRT1 expression, resulting in the senescence of osteoblasts 40 . Relatively few studies have been focused on the AA metabolite‐mediated differentiation and development of chondrocytes by AA metabolites.…”

Section: Aa Metabolism In Human Health and Diseasesmentioning

confidence: 99%

“… 39 LTD‐4, another leukotriene metabolite, significantly increases the expression of p53, p21, and plasminogen activator inhibitor‐1 (PAI‐1), as well as the activity of senescence‐associated β‐galactosidase (SA‐β‐Gal), with commensurate reduction in SIRT1 expression, resulting in the senescence of osteoblasts. 40 Relatively few studies have been focused on the AA metabolite‐mediated differentiation and development of chondrocytes by AA metabolites. One study showed that PGE‐2 inhibited the expression of the differentiation‐related genes in chondrocytes, such as collagen‐X (col‐X), vascular endothelial growth factor (VEGF), matrix metalloproteinase‐13 (MMP‐13), and ALP, in a dose‐dependent manner, resulting in inhibited chondrocyte maturation.…”

Section: Aa Metabolism In Human Health and Diseasesmentioning

confidence: 99%

Arachidonic acid metabolism in health and disease

Zhang,

Liu,

Sun

et al. 2023

MedComm

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Arachidonic acid (AA), an n‐6 essential fatty acid, is a major component of mammalian cells and can be released by phospholipase A2. Accumulating evidence indicates that AA plays essential biochemical roles, as it is the direct precursor of bioactive lipid metabolites of eicosanoids such as prostaglandins, leukotrienes, and epoxyeicosatrienoic acid obtained from three distinct enzymatic metabolic pathways: the cyclooxygenase pathway, lipoxygenase pathway, and cytochrome P450 pathway. AA metabolism is involved not only in cell differentiation, tissue development, and organ function but also in the progression of diseases, such as hepatic fibrosis, neurodegeneration, obesity, diabetes, and cancers. These eicosanoids are generally considered proinflammatory molecules, as they can trigger oxidative stress and stimulate the immune response. Therefore, interventions in AA metabolic pathways are effective ways to manage inflammatory‐related diseases in the clinic. Currently, inhibitors targeting enzymes related to AA metabolic pathways are an important area of drug discovery. Moreover, many advances have also been made in clinical studies of AA metabolic inhibitors in combination with chemotherapy and immunotherapy. Herein, we review the discovery of AA and focus on AA metabolism in relation to health and diseases. Furthermore, inhibitors targeting AA metabolism are summarized, and potential clinical applications are discussed.

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Leukotriene D4 induces cellular senescence in osteoblasts

Cited by 10 publications

References 31 publications

Senescence-associated secretory phenotype and its impact on oral immune homeostasis

Senescence-associated secretory phenotype and its impact on oral immune homeostasis

Age-related alterations in metabolome and microbiome provide insights in dietary transition in giant pandas

Arachidonic acid metabolism in health and disease

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