Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption

Yang, Xiao; Gandhi, Chintan; Rahman, Matlubur; Appleford, Mark R.; Sun, Lian; Wang, Xiaodu

doi:10.1007/s00223-015-0042-1

Cited by 9 publications

(6 citation statements)

References 32 publications

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“…Here, our study rst observed that M1 macrophages prefer to highly express the above osteoclast-related markers, proving that M1 macrophages have greater osteoclastogenesis potential, which is consistent with the research of Huang et al [27]. To date, some reports have been put to con rm that AGEs are related to osteoclasts metabolism, but its speci c role in regulating bone resorption is not clear [28,29]. We then examined the role of AGEs in the differentiation of M1 macrophages into osteoclasts.…”

Section: Discussionsupporting

confidence: 90%

Notch/NICD/RBP-J Signaling Axis Regulates M1 Polarization of Macrophages Mediated by Advanced Glycation End Products

Tan¹,

Xu²,

Ding³

et al. 2021

Preprint

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Advanced glycation end products (AGEs) aggregation and macrophages polarization both play essential roles in degenerative bone diseases caused by aging or diabetes, such as senile or diabetic osteoporosis. Here, we aimed to understand the involvement and potential mechanism of AGEs in macrophages polarization and osteoclastogenesis. We found that RAW264.7 macrophages treated with AGEs highly expressed M1-associated genes and surface antigen markers CD86, and released a large amount of NO to the extracellular environment. Through the detection of osteoclast-related markers and TRAP staining, we revealed that the osteoclastogenesis of M1 macrophages could be markedly enhanced by AGEs. To explore the potential mechanisms of AGEs-mediated M1 polarization, we first demonstrated that AGEs effectively activated the transduction of Notch signaling pathway, including nuclear translocation of NICD1. Subsequently, it was observed that the M1 polarization effects induced by AGEs were significantly mitigated, when γ-secretase inhibitor DAPT and siRNA targeting silencing RBP-J were applied to block the signal transduction of Notch. In conclusion, our findings revealed a series of phenomena that AGEs induce macrophage M1 polarization and enhance its osteoclastogenesis ability, and Notch/NICD/RBP-J signaling axis is involved in the regulation of this polarization process.

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Section: Discussionsupporting

confidence: 90%

Notch/NICD/RBP-J Signaling Axis Regulates M1 Polarization of Macrophages Mediated by Advanced Glycation End Products

Tan¹,

Xu²,

Ding³

et al. 2021

Preprint

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“…65 Nevertheless, reactive oxygen species may induce cell apoptosis and damage to DNA and structural components of cells and matrix. 66,67 Increased mitochondrial generation of reactive oxygen species has been linked to greater periodontitis in diabetics. 68 Diabetic patients have an increased number of inducible nitric oxide synthase-positive cells in the periodontium and levels of lipid peroxides are elevated in the gingival crevicular fluid of type 2 diabetes mellitus patients.…”

Section: Iab E Te S Peri Odontal D Is E a S E S And Infl Ammamentioning

confidence: 99%

“…However, this hypothesis has been recently challenged . Nevertheless, reactive oxygen species may induce cell apoptosis and damage to DNA and structural components of cells and matrix . Increased mitochondrial generation of reactive oxygen species has been linked to greater periodontitis in diabetics .…”

Section: Diabetes Periodontal Diseases and Inflammationmentioning

confidence: 99%

The impact of diabetes on periodontal diseases

Graves

Ding

Yang

2019

Periodontology 2000

237

172

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The susceptibility and severity of periodontal diseases is made more severe by diabetes, with the impact on the disease process inversely proportional to the level of glycemic control. Although type 1 diabetes mellitus and type 2 diabetes mellitus have different etiologies, and their impact on bone is not identical, they share many of the same complications. Studies in animals and humans agree that both forms of diabetes increase inflammatory events in periodontal tissue, impair new bone formation, and increase expression of RANKL in response to bacterial challenge. High levels of glucose, reactive oxygen species, and advanced glycation end‐products are found in the periodontium of diabetic individuals and lead to increased activation of nuclear factor‐kappa B and expression of inflammatory cytokines such as tumor necrosis factor and interleukin‐1. Studies in animals, moreover, suggest that there are multiple cell types in periodontal tissues that are affected by diabetes, including leukocytes, vascular cells, mesenchymal stem cells, periodontal ligament fibroblasts, osteoblasts, and osteocytes. The etiology of periodontal disease involves the host response to bacterial challenge that is affected by diabetes, which increases the expression of RANKL and reduces coupled bone formation. In addition, the inflammatory response also modifies the oral microbiota to render it more pathogenic, as demonstrated by increased inflammation and bone loss in animals where bacteria are transferred from diabetic donors to germ‐free hosts compared with transfer from normoglycemic donors. This approach has the advantage of not relying upon limited knowledge of the specific bacterial taxa to determine pathogenicity, and examines the overall impact of the microbiota rather than the presumed pathogenicity of a few bacterial groups. Thus, animal studies have provided new insights into pathogenic mechanisms that identify cause‐and‐effect relationships that are difficult to perform in human studies.

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“…Patients with T2D have higher levels of AGEs due to hyperglycemia, which can also increase the production of inflammatory cytokines and reactive oxygen species, setting off a vicious cycle of chronic inflammation and bone resorption ( 59 ). Activating of RAGE in both osteoclasts ( 60 , 61 ) and osteoblasts ( 46 , 62 ) could induce up-regulation of pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α, which could directly affect bone homeostasis ( 63 , 64 ). Accumulating evidence indicates that the TGF-β also plays an important role in the osteogenic progress affected by AGEs, especially biologically potent AGE2 and AGE3 ( 65 , 66 ).…”

Section: Discussionmentioning

confidence: 99%

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

Gao

Liu²,

Pan³

et al. 2022

Front. Endocrinol.

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ObjectiveThe objective of this study was to analyze the quantitative association between advanced glycation end products (AGEs) and adjusted FRAX by rheumatoid arthritis (FRAX-RA) in postmenopausal type 2 diabetic (T2D) patients. The optimal cutoff value of AGEs was also explored, which was aimed at demonstrating the potential value of AGEs on evaluating osteoporotic fracture risk in postmenopausal T2D patients.MethodsWe conducted a cross-sectional study including 366 postmenopausal participants (180 T2D patients [DM group] and 186 non-T2D individuals [NDM group]). All the subjects in each group were divided into three subgroups according to BMD. Physical examination, dual-energy x-ray absorptiometry (DXA), and serum indicators (including serum AGEs, glycemic parameters, bone turnover markers and inflammation factors) were examined. The relationship between FRAX-RA, serum laboratory variables, and AGEs were explored. The optimal cutoff value of AGEs to predict the risk of osteoporotic fracture was also investigated.ResultsAdjusting the FRAX values with rheumatoid arthritis (RA) of T2D patients reached a significantly increased MOF-RA and an increasing trend of HF-RA. AGEs level was higher in the DM group compared to the NDMs, and was positively correlated with MOF-RA (r=0.682, P<0.001) and HF-RA (r=0.677, P<0.001). The receiver operating characteristic curve analysis revealed that the area under the curve was 0.804 (P<0.001), and the optimal AGEs cut-off value was 4.156mmol/L. Subgroup analysis for T2D patients revealed an increase in TGF-β, IL-6 and SCTX in the osteoporosis group, while a decreased PINP in the osteoporosis group compared to the other two subgroups. AGEs were positively associated with FBG, HbA1c, HOMA-IR, S-CTX, IL-6 and TGF-β in T2D patients, and negatively associated with PINP.ConclusionsRA-adjusted FRAX is a relevant clinical tool in evaluating fracture risk of postmenopausal T2D patients. Our study analyzed the relationship between AGEs and FRAX-RA, and explored the threshold value of AGEs for predicting fracture risk in postmenopausal T2D patients. AGEs were also associated with serum bone turnover markers and inflammation factors, indicating that the increasing level of AGEs in postmenopausal T2D patients accelerated the expression of inflammatory factors, which led to bone metabolism disorders and a higher risk of osteoporotic fractures.

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Age-Related Effects of Advanced Glycation End Products (Ages) in Bone Matrix on Osteoclastic Resorption

Cited by 9 publications

References 32 publications

Notch/NICD/RBP-J Signaling Axis Regulates M1 Polarization of Macrophages Mediated by Advanced Glycation End Products

Notch/NICD/RBP-J Signaling Axis Regulates M1 Polarization of Macrophages Mediated by Advanced Glycation End Products

The impact of diabetes on periodontal diseases

The role of advanced glycation end products in fracture risk assessment in postmenopausal type 2 diabetic patients

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