Advanced Glycation End Products, Bone Health, and Diabetes Mellitus

Abstract

Advanced glycation end products (AGEs), the compounds resulting from the non-enzymatic glycosylation between reducing sugars and proteins, are derived from food or produced de novo. Over time, more and more endogenous and exogenous AGEs accumulate in various organs such as the liver, kidneys, muscle, and bone, threatening human health. Among these organs, bone is most widely reported. AGEs accumulating in bone reduce bone strength by participating in bone structure formation and breaking bone homeostasis by binding their receptors to alter the proliferation, differentiation, and apoptosis of cells involved in bone remodeling. In this review, we summarize the research about the effects of AGEs on bone health and highlight their associations with bone health in diabetes patients to provide some clues toward the discovery of new treatment and prevention strategies for bone-related diseases caused by AGEs.

Key words

Advanced glycation end products - Bone remodeling - Bone fragility - Diabetes

Publikationsverlauf

Eingereicht: 09. Februar 2022
Eingereicht: 11. Mai 2022

Angenommen: 16. Mai 2022

Artikel online veröffentlicht:
18. Oktober 2022

• References

• 1 Sanajou D, Ghorbani Haghjo A, Argani H. et al. AGE-RAGE axis blockade in diabetic nephropathy: Current status and future directions. Eur J Pharmacol 2018; 833: 158-164
• 2 Frimat M, Daroux M, Litke R. et al. Kidney, heart and brain: Three organs targeted by ageing and glycation. Clin Sci (Lond) 2017; 131: 1069-1092
• 3 Chao PC, Huang CN, Hsu CC. et al. Association of dietary AGEs with circulating AGEs, glycated LDL, IL-1alpha and MCP-1 levels in type 2 diabetic patients. Eur J Nutr 2010; 49: 429-434
• 4 Singh R, Barden A, Mori T. et al. Advanced glycation end-products: A review. Diabetologia 2001; 44: 129-146
• 5 Cerami C, Founds H, Nicholl I. et al. Tobacco smoke is a source of toxic reactive glycation products. Proc Natl Acad Sci U S A 1997; 94: 13915-13920
• 6 Ravichandran G, Lakshmanan DK, Raju K. et al. Food advanced glycation end products as potential endocrine disruptors: An emerging threat to contemporary and future generation. Environ Int 2019; 123: 486-500
• 7 Kumar Pasupulati A, Chitra PS, Reddy GB. Advanced glycation end products mediated cellular and molecular events in the pathology of diabetic nephropathy. Biomol Concepts 2016; 7: 293-309
• 8 Chappey O, Dosquet C, Wautier MP. et al. Advanced glycation end products, oxidant stress and vascular lesions. Eur J Clin Invest 1997; 27: 97-108
• 9 Suzuki A, Yabu A, Nakamura H. Advanced glycation end products in musculoskeletal system and disorders. Methods. 2020
• 10 Wisotzky J, Sommer M, Schubert K. et al. Accumulation of AGE (advanced glycosylation end-products) in the aging process, in diabetes mellitus and in chronic renal failure. Med Klin 1996; 91: 454-457
• 11 Deluyker D, Lize E, Bito V. Advanced glycation end products (AGEs) and cardiovascular dysfunction: Focus on high molecular weight AGEs. Amino Acids 2017; 49: 1535-1541
• 12 Franke S, Sommer M, Ruster C. et al. Advanced glycation end products induce cell cycle arrest and proinflammatory changes in osteoarthritic fibroblast-like synovial cells. Arthritis Res Ther 2009; 11: R136
• 13 Semba RD, Nicklett EJ, Ferrucci L. Does accumulation of advanced glycation end products contribute to the aging phenotype?. J Gerontol A Biol Sci Med Sci 2010; 65: 963-975
• 14 Costantini S, Conte C. Bone health in diabetes and prediabetes. World J Diabetes 2019; 10: 421-445
• 15 Wang JF, Lee MS, Tsai TL. et al. Bone morphogenetic protein-6 attenuates type 1 diabetes mellitus-associated bone loss. Stem Cells Transl Med 2019; 8: 522-534
• 16 Takeuchi M.. Serum levels of toxic AGEs (TAGE) may be a promising novel biomarker for the onset/progression of lifestyle-related diseases. Diagnostics (Basel) 2016; 6
• 17 Saremi A, Howell S, Schwenke DC. et al. Advanced glycation end products, oxidation products, and the extent of atherosclerosis during the VA diabetes trial and follow-up study. Diabetes Care 2017; 40: 591-598
• 18 Hadjidakis DJ, Androulakis II. Bone remodeling. Ann N Y Acad Sci 2006; 1092: 385-396
• 19 Sanguineti R, Puddu A, Mach F. et al. Advanced glycation end products play adverse proinflammatory activities in osteoporosis. Mediators Inflamm 2014; 2014: 975872
• 20 Saito M, Fujii K, Mori Y. et al. Role of collagen enzymatic and glycation induced cross-links as a determinant of bone quality in spontaneously diabetic WBN/Kob rats. Osteoporos Int 2006; 17: 1514-1523
• 21 Yamamoto M, Sugimoto T. Advanced glycation end products, diabetes, and bone strength. Curr Osteoporos Rep 2016; 14: 320-326
• 22 Tanaka K, Yamagata K, Kubo S. et al. Glycolaldehyde-modified advanced glycation end-products inhibit differentiation of human monocytes into osteoclasts via upregulation of IL-10. Bone 2019; 128: 115034
• 23 Aikawa E, Fujita R, Asai M. et al. Receptor for advanced glycation end products-mediated signaling impairs the maintenance of bone marrow mesenchymal stromal cells in diabetic model mice. Stem Cells Dev 2016; 25: 1721-1732
• 24 Alikhani M, Alikhani Z, Boyd C. et al. Advanced glycation end products stimulate osteoblast apoptosis via the MAP kinase and cytosolic apoptotic pathways. Bone 2007; 40: 345-353
• 25 Rasmussen LM, Tarnow L, Hansen TK. et al. Plasma osteoprotegerin levels are associated with glycaemic status, systolic blood pressure, kidney function and cardiovascular morbidity in type 1 diabetic patients. Eur J Endocrinol 2006; 154: 75-81
• 26 Grimsby JL, Lucero HA, Trackman PC. et al. Role of lysyl oxidase propeptide in secretion and enzyme activity. J Cell Biochem 2010; 111: 1231-1243
• 27 Banse X, Sims TJ, Bailey AJ. Mechanical properties of adult vertebral cancellous bone: Correlation with collagen intermolecular cross-links. J Bone Miner Res 2002; 17: 1621-1628
• 28 Garnero P, Borel O, Gineyts E. et al. Extracellular post-translational modifications of collagen are major determinants of biomechanical properties of fetal bovine cortical bone. Bone 2006; 38: 300-309
• 29 Vashishth D. The role of the collagen matrix in skeletal fragility. Curr Osteoporos Rep 2007; 5: 62-66
• 30 Nagaoka H, Mochida Y, Atsawasuwan P. et al. 1,25(OH)2D3 regulates collagen quality in an osteoblastic cell culture system. Biochem Biophys Res Commun 2008; 377: 674-678
• 31 Karim L, Vashishth D. Heterogeneous glycation of cancellous bone and its association with bone quality and fragility. PLoS ONE 2012; 7: e35047
• 32 Monnier VM, Sell DR, Nagaraj RH. et al. Maillard reaction-mediated molecular damage to extracellular matrix and other tissue proteins in diabetes, aging, and uremia. Diabetes 1992; 41: 36-41
• 33 Saito M, Marumo K. Bone quality in diabetes. Front Endocrinol (Lausanne) 2013; 4: 72
• 34 Li W, Ling W, Teng X. et al. Effect of advanced glycation end products, extracellular matrix metalloproteinase inducer and matrix metalloproteinases on type-I collagen metabolism. Biomed Rep 2016; 4: 691-693
• 35 Valcourt U, Merle B, Gineyts E. et al. Non-enzymatic glycation of bone collagen modifies osteoclastic activity and differentiation. J Biol Chem 2007; 282: 5691-5703
• 36 Everts V, Korper W, Docherty AJ. et al. Matrix metalloproteinase inhibitors block osteoclastic resorption of calvarial bone but not the resorption of long bone. Ann N Y Acad Sci 1999; 878: 603-606
• 37 Zhang H, Luo XH, Xie H. et al. Age-related changes serum levels of MMP-1 and MMP-2 in women: their relationship with bone biochemical markers and bone mineral density. Zhonghua nei ke za zhi 2006; 45: 306-309
• 38 Sanguineti R, Storace D, Monacelli F. et al. Pentosidine effects on human osteoblasts in vitro. Ann N Y Acad Sci 2008; 1126: 166-172
• 39 Yang X, Mostafa AJ, Appleford M. et al. Bone Formation is Affected by matrix advanced glycation end products (AGEs) In Vivo. Calcif Tissue Int 2016; 99: 373-383
• 40 Gefter JV, Shaufl AL, Fink MP. et al. Comparison of distinct protein isoforms of the receptor for advanced glycation end-products expressed in murine tissues and cell lines. Cell Tissue Res 2009; 337: 79-89
• 41 Kume S, Kato S, Yamagishi S. et al. Advanced glycation end-products attenuate human mesenchymal stem cells and prevent cognate differentiation into adipose tissue, cartilage, and bone. J Bone Miner Res 2005; 20: 1647-1658
• 42 Franke S, Rüster C, Pester J. et al. Advanced glycation end products affect growth and function of osteoblasts. Clin Exp Rheumatol 2011; 29: 650-660
• 43 Momma H, Niu K, Kobayashi Y. et al. Skin advanced glycation end-product accumulation is negatively associated with calcaneal osteo-sono assessment index among non-diabetic adult Japanese men. Osteoporos Int 2012; 23: 1673-1681
• 44 Miyata T, Notoya K, Yoshida K. et al. Advanced glycation end products enhance osteoclast-induced bone resorption in cultured mouse unfractionated bone cells and in rats implanted subcutaneously with devitalized bone particles. J Am Soc Nephrol 1997; 8: 260-270
• 45 Li Z, Li C, Zhou Y. et al. Advanced glycation end products biphasically modulate bone resorption in osteoclast-like cells. Am J Physiol Endocrinol Metab 2016; 310: E355-E366
• 46 Asadipooya K, EMJJotES Uy. Advanced glycation end products (AGEs), Receptor for AGEs, diabetes, and bone: Review of the literature. J Endocr Soc 2019; 3: 1799-1818
• 47 Tanaka K, Yamaguchi T, Kaji H. et al. Advanced glycation end products suppress osteoblastic differentiation of stromal cells by activating endoplasmic reticulum stress. Biochem Biophys Res Commun 2013; 438: 463-467
• 48 Lu C, He JC, Cai W. et al. Advanced glycation endproduct (AGE) receptor 1 is a negative regulator of the inflammatory response to AGE in mesangial cells. Proc Natl Acad Sci U S A 2004; 101: 11767-11772
• 49 Dumitriu IE, Baruah P, Valentinis B. et al. Release of high mobility group box 1 by dendritic cells controls T cell activation via the receptor for advanced glycation end products. J Immunol 2005; 174: 7506-7515
• 50 Karlsson S, Kowanetz K, Sandin A. et al. Loss of T-cell protein tyrosine phosphatase induces recycling of the platelet-derived growth factor (PDGF) beta-receptor but not the PDGF alpha-receptor. Mol Biol Cell 2006; 17: 4846-4855
• 51 Caplan AI, Correa D. PDGF in bone formation and regeneration: New insights into a novel mechanism involving MSCs. J Orthop Res 2011; 29: 1795-1803
• 52 Okazaki K, Yamaguchi T, Tanaka K. et al. Advanced glycation end products (AGEs), but not high glucose, inhibit the osteoblastic differentiation of mouse stromal ST2 cells through the suppression of osterix expression, and inhibit cell growth and increasing cell apoptosis. Calcif Tissue Int 2012; 91: 286-296
• 53 Ding KH, Wang ZZ, Hamrick MW. et al. Disordered osteoclast formation in RAGE-deficient mouse establishes an essential role for RAGE in diabetes related bone loss. Biochem Biophys Res Commun 2006; 340: 1091-1097
• 54 Li G, Xu J, Li Z.. Receptor for advanced glycation end products inhibits proliferation in osteoblast through suppression of Wnt, PI3K and ERK signaling. Biochem Biophys Res Commun 2012; 423: 684-689
• 55 Meng HZ, Zhang WL, Liu F. et al. Advanced glycation end products affect osteoblast proliferation and function by modulating autophagy via the receptor of advanced glycation end products/Raf protein/mitogen-activated protein kinase/extracellular signal-regulated kinase kinase/extracellular signal-regulated kinase (RAGE/Raf/MEK/ERK) pathway. J Biol Chem 2015; 290: 28189-28199
• 56 Weinberg E, Maymon T, Weinreb MJJoME.. AGEs induce caspase-mediated apoptosis of rat BMSCs via TNFα production and oxidative stress. J Mol Endocrinol 2014; 52: 67-76
• 57 Tanaka K, Yamaguchi T, Kanazawa I. et al. Effects of high glucose and advanced glycation end products on the expressions of sclerostin and RANKL as well as apoptosis in osteocyte-like MLO-Y4-A2 cells. Biochem Biophys Res Commun 2015; 461: 193-199
• 58 Wang Y, Pennock SD, Chen X. et al. Platelet-derived growth factor receptor-mediated signal transduction from endosomes. J Biol Chem 2004; 279: 8038-8046
• 59 Caverzasio J, Biver E, Thouverey C.. Predominant role of PDGF receptor transactivation in Wnt3a-induced osteoblastic cell proliferation. J Bone Miner Res 2013; 28: 260-270
• 60 Demers LM, Costa L, Chinchilli VM. et al. Biochemical markers of bone turnover in patients with metastatic bone disease. Clinical Chemistry 1995; 41: 1489-1494
• 61 Verron E, Gauthier O, Janvier P. et al. In vivo bone augmentation in an osteoporotic environment using bisphosphonate-loaded calcium deficient apatite. Biomaterials 2010; 31: 7776-7784
• 62 Shakibaei M, Buhrmann C. Mobasheri AJJoBC. Resveratrol-mediated SIRT-1 interactions with p300 modulate receptor activator of NF-κB ligand (RANKL) activation of NF-κB signaling and inhibit osteoclastogenesis in bone-derived cells. J Biol Chem 2011; 286: 11492-11505
• 63 An J, Yang H, Zhang Q. et al. Natural products for treatment of osteoporosis: The effects and mechanisms on promoting osteoblast-mediated bone formation. Life Sci 2016; 147: 46-58
• 64 Krall EA, Dawson-Hughes B.. Heritable and life-style determinants of bone mineral density. J Bone Miner Res 2009; 8: 1-9
• 65 Pocock NA, Eisman JA, Hopper JL. et al. Genetic determinants of bone mass in adults. A twin study. J Clin Invest 1987; 80: 706-710
• 66 Seeman E. Invited Review: Pathogenesis of osteoporosis. J Appl Physiol 2003; 95: 2142-2151
• 67 Vlassara H. Recent progress in advanced glycation end products and diabetic complications. Diabetes 1997; 46: S19-S25
• 68 Hein G, Wiegand R, Lehmann G. et al. Advanced glycation end-products pentosidine and N epsilon-carboxymethyllysine are elevated in serum of patients with osteoporosis. Rheumatology (Oxford) 2003; 42: 1242-1246
• 69 Hein G, Weiss C, Lehmann G. et al. Advanced glycation end product modification of bone proteins and bone remodelling: Hypothesis and preliminary immunohistochemical findings. Ann Rheum Dis 2006; 65: 101-104
• 70 Viguet-Carrin S, Follet H, Gineyts E. et al. Association between collagen cross-links and trabecular microarchitecture properties of human vertebral bone. Bone 2010; 46: 342-347
• 71 Saito M, Kida Y, Kato S. et al. Diabetes, collagen, and bone quality. Curr Osteoporos Rep 2014; 12: 181-188
• 72 Tang SY, Vashishth D.. The relative contributions of non-enzymatic glycation and cortical porosity on the fracture toughness of aging bone. J Biomech 2011; 44: 330-336
• 73 Luhmann T, Germershaus O, Groll J. et al. Bone targeting for the treatment of osteoporosis. J Control Release 2012; 161: 198-213
• 74 Shen G, Ren H, Shang Q. et al. Autophagy as a target for glucocorticoid-induced osteoporosis therapy. Cell Mol Life Sci 2018; 75: 2683-2693
• 75 McCarthy AD, Etcheverry SB, Bruzzone L. et al. Non-enzymatic glycosylation of a type I collagen matrix: Effects on osteoblastic development and oxidative stress. BMC Cell Biol 2001; 2: 16
• 76 Janghorbani M, Feskanich D, Willett WC. et al. Prospective study of diabetes and risk of hip fracture: The Nurses' Health Study. Diabetes Care 2006; 29: 1573-1578
• 77 Thong EP, Herath M, Weber DR. et al. Fracture risk in young and middle-aged adults with type 1 diabetes mellitus: A systematic review and meta-analysis. Clin Endocrinol (Oxf) 2018; 89: 314-323
• 78 Vestergaard P.. Discrepancies in bone mineral density and fracture risk in patients with type 1 and type 2 diabetes--a meta-analysis. Osteoporos Int 2007; 18: 427-444
• 79 Hamann C, Kirschner S, Gunther KP. et al. Bone, sweet bone--osteoporotic fractures in diabetes mellitus. Nat Rev Endocrinol 2012; 8: 297-305
• 80 Oei L, Rivadeneira F, Zillikens MC. et al. Diabetes, diabetic complications, and fracture risk. Curr Osteoporos Rep 2015; 13: 106-115
• 81 Gregorio F, Cristallini S, Santeusanio F. et al. Osteopenia associated with non-insulin-dependent diabetes mellitus: What are the causes?. Diabetes Res Clin Pract 1994; 23: 43-54
• 82 Santana RB, Xu L, Chase HB. et al. A role for advanced glycation end products in diminished bone healing in type 1 diabetes. Diabetes 2003; 52: 1502-1510
• 83 Arif Z, Neelofar K, Arfat MY. et al. Hyperglycemia induced reactive species trigger structural changes in human serum albumin of type 1 diabetic subjects. Int J Biol Macromol 2018; 107: 2141-2149
• 84 Willett TL, Pasquale J, Grynpas MD.. Collagen modifications in postmenopausal osteoporosis: Advanced glycation endproducts may affect bone volume, structure and quality. Curr Osteoporos Rep 2014; 12: 329-337
• 85 Suga T, Iso T, Shimizu T. et al. Activation of receptor for advanced glycation end products induces osteogenic differentiation of vascular smooth muscle cells. J Atheroscler Thromb 2011; 18: 670-683
• 86 Fukami A, Adachi H, Yamagishi S. et al. Factors associated with serum high mobility group box 1 (HMGB1) levels in a general population. Metabolism 2009; 58: 1688-1693
• 87 Yamamoto M, Yamaguchi T, Yamauchi M. et al. Low serum level of the endogenous secretory receptor for advanced glycation end products (esRAGE) is a risk factor for prevalent vertebral fractures independent of bone mineral density in patients with type 2 diabetes. Diabetes Care 2009; 32: 2263-2268
• 88 Sroga GE, Vashishth D.. Controlled formation of carboxymethyllysine in bone matrix through designed glycation reaction. JBMR Plus 2021; 5: e10548
• 89 Asadipooya K, Uy EM. Advanced glycation end products (AGEs), receptor for AGEs, diabetes, and bone: Review of the literature. Journal of the Endocrine Society 2019; 3: 1799-1818
• 90 Yamaguchi T. Bone metabolism and cardiovascular function update. Lifestyle-related common diseases and osteoporosis. Clin Calcium 2014; 24: 21-26