Advanced Glycation End Products (AGEs), Receptor for AGEs, Diabetes, and Bone: Review of the Literature

Asadipooya, Kamyar; Uy, Edilfavia Mae

doi:10.1210/js.2019-00160

Cited by 160 publications

(114 citation statements)

References 111 publications

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“…An increase of RAGE ligand signaling is related to different pathologies characterized by reduced bone mass/strength, including diabetes, cancer, cardiovascular disease, and neurodegeneration [32]. Although RAGE expression is upregulated in inflammatory pathological conditions, it has been suggested that RAGE signaling may have also a role in inflammation resolution and tissue repair [33]. The harmful effects of the RAGE ligands AGEs on osteoblast viability and activity have been identified [11].…”

Section: Ragementioning

confidence: 99%

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review

et al. 2020

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Alarmins are endogenous mediators released by cells following insults or cell death to alert the host’s innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiological processes and inflammatory diseases including osteoporosis. The aim of the review was to evaluate the role of alarmins in osteoporosis. A bibliographic search of the published scientific literature regarding the role of alarmins in osteoporosis was organized independently by two researchers in the following scientific databases: Pubmed, Scopus, and Web of Science. The keywords used were combined as follows: “alarmins and osteoporosis”, “RAGE and osteoporosis”, “HMGB1 and osteoporosis”, “IL-1 and osteoporosis”, “IL 33 and osteopororsis”, “S100s protein and osteoporosis”. The information was summarized and organized in the present review. We highlight the emerging roles of alarmins in various bone remodeling processes involved in the onset and development of osteoporosis, as well as their potential role as biomarkers of osteoporosis severity and progression. Findings of the research suggest a potential use of alarmins as pharmacological targets in future therapeutic strategies aimed at preventing bone loss and fragility fractures induced by aging and inflammatory diseases.

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Section: Ragementioning

confidence: 99%

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review

et al. 2020

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“…Diabetic complications and osteoporotic fracture are chronic diseases that share several features including genetic susceptibility and environmental factors [11]. In addition, both glycemic and bone homeostasis are known to be under the influence of common regulatory factors such as insulin, peroxisome proliferator-activated receptor-gamma, gastrointestinal hormones, and osteocalcin [11][12][13]. Advanced glycation end products (AGE) accumulate in diabetic dysfunction and bone homeostasis [12].…”

Section: Introductionmentioning

confidence: 99%

“…In addition, both glycemic and bone homeostasis are known to be under the influence of common regulatory factors such as insulin, peroxisome proliferator-activated receptor-gamma, gastrointestinal hormones, and osteocalcin [11][12][13]. Advanced glycation end products (AGE) accumulate in diabetic dysfunction and bone homeostasis [12]. Accordingly, the association between diabetes mellitus and bone health has long been a matter of debate.…”

Section: Introductionmentioning

confidence: 99%

“…However, several studies have shown that diabetic bone is characterized by abnormal alterations in bone metabolism, decreased bone mineral content and density, increased fracture rate, and delayed fracture healing [13][14][15]. Furthermore, in diabetes mellitus, bone turnover is reduced or disrupted in parallel with increased risk of bone fractures, in which bone formation declines with reduced mineralization and bone cell number [12,16]. In general, patients with diabetes carry decreased levels of biochemical markers of bone turnover [13,17].…”

Section: Introductionmentioning

confidence: 99%

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Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

et al. 2020

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Accumulating evidence demonstrates that the risk of osteoporotic fractures increases in patients with diabetes mellitus. Thus, diabetes-induced bone fragility has recently been recognized as a diabetic complication. As the fracture risk is independent of the reduction in bone mineral density, deterioration in bone quality may be the main cause of bone fragility. Coumarin exists naturally in many plants as phenylpropanoids and is present in tonka beans in significantly high concentrations. This study investigated whether coumarin ameliorated the impaired bone turnover and remodeling under diabetic condition. The in vitro study employed murine macrophage Raw 264.7 cells differentiated to multinucleated osteoclasts with receptor activator of nuclear factor-κΒ ligand (RANKL) in the presence of 33 mM glucose and 1–20 μM coumarin for five days. In addition, osteoblastic MC3T3-E1 cells were exposed to 33 mM glucose for up to 21 days in the presence of 1–20 μM coumarin. High glucose diminished tartrate-resistant acid phosphatase activity and bone resorption in RANKL-differentiated osteoclasts, accompanying a reduction of cathepsin K induction and actin ring formation. In contrast, coumarin reversed the defective osteoclastogenesis in diabetic osteoclasts. Furthermore, high glucose diminished alkaline phosphatase activity and collagen type 1 induction of osteoblasts, which was strongly enhanced by submicromolar levels of coumarin to diabetic cells. Furthermore, coumarin restored the induction of RANK and osteoprotegerin in osteoclasts and osteoblasts under glucotoxic condition, indicating a tight coupling of osteoclastogenesis and osteoblastogenesis. Coumarin ameliorated the impaired bone turnover and remodeling in diabetic osteoblasts and osteoclasts by suppressing the interaction between advanced glycation end product (AGE) and its receptor (RAGE). Therefore, coumarin may restore optimal bone turnover of osteoclasts and osteoblasts by disrupting the hyperglycemia-mediated AGE–RAGE interaction.

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“…The activation of RAGE induces an inflammatory cascade that starts with activation of a transcription factor nuclear factor-kappa B (NF-κB) that promotes the expression of proinflammatory cytokines, growth factor, and adhesive molecules [12,13]. Specifically, the engagement of RAGE increases oxidative stress by activating NADPH oxidase that also increases in NF-κB stimulation [14].…”

Section: Introductionmentioning

confidence: 99%

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

Perrone

Giovino

Benny

et al. 2020

Oxidative Medicine and Cellular Longevity

294

219

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The advanced glycation end products (AGEs) are organic molecules formed in any living organisms with a great variety of structural and functional properties. They are considered organic markers of the glycation process. Due to their great heterogeneity, there is no specific test for their operational measurement. In this review, we have updated the most common chromatographic, colorimetric, spectroscopic, mass spectrometric, and serological methods, typically used for the determination of AGEs in biological samples. We have described their signaling and signal transduction mechanisms and cell epigenetic effects. Although mass spectrometric analysis is not widespread in the detection of AGEs at the clinical level, this technique is highly promising for the early diagnosis and therapeutics of diseases caused by AGEs. Protocols are available for high-resolution mass spectrometry of glycated proteins although they are characterized by complex machine management. Simpler procedures are available although much less precise than mass spectrometry. Among them, immunochemical tests are very common since they are able to detect AGEs in a simple and immediate way. In these years, new methodologies have been developed using an in vivo novel and noninvasive spectroscopic methods. These methods are based on the measurement of autofluorescence of AGEs. Another method consists of detecting AGEs in the human skin to detect chronic exposure, without the inconvenience of invasive methods. The aim of this review is to compare the different approaches of measuring AGEs at a clinical perspective due to their strict association with oxidative stress and inflammation.

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Advanced Glycation End Products (AGEs), Receptor for AGEs, Diabetes, and Bone: Review of the Literature

Cited by 160 publications

References 111 publications

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review

Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review

Coumarin Ameliorates Impaired Bone Turnover by Inhibiting the Formation of Advanced Glycation End Products in Diabetic Osteoblasts and Osteoclasts

Advanced Glycation End Products (AGEs): Biochemistry, Signaling, Analytical Methods, and Epigenetic Effects

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