Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction

ABSTRACT It has been a challenge to establish a link between specific advanced glycation end products (AGEs) as causal agents of different pathologies and age‐related diseases, primarily because of the lack of suitable in vitro experimental strategies facilitating increased formation of a specific A...

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Autores principales:	Grażyna E. Sroga, Deepak Vashishth
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	BONE MATRIX CARBOXYMETHYLLYSINE DESIGNED IN VITRO GLYCATION HUMAN OXIDATIVE/CARBONYL STRESS Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
Acceso en línea:	https://doaj.org/article/d08c99eedae841db8cb94346a00ca5cc
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spelling	oai:doaj.org-article:d08c99eedae841db8cb94346a00ca5cc2021-11-04T12:00:57ZControlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction2473-403910.1002/jbm4.10548https://doaj.org/article/d08c99eedae841db8cb94346a00ca5cc2021-11-01T00:00:00Zhttps://doi.org/10.1002/jbm4.10548https://doaj.org/toc/2473-4039ABSTRACT It has been a challenge to establish a link between specific advanced glycation end products (AGEs) as causal agents of different pathologies and age‐related diseases, primarily because of the lack of suitable in vitro experimental strategies facilitating increased formation of a specific AGE, here carboxymethyllysine (CML), over other AGEs under controlled conditions. CML is of considerable importance to various oxidative stress–related diseases, because in vivo formation of this AGE is connected with cellular oxidative/carbonyl metabolism. The mechanistic implications of CML accumulation in bone remain to be elucidated. To facilitate such studies, we developed a new in vitro strategy that allows preferential generation of CML in bone matrix over other AGEs. Using bone samples from human donors of different age (young, middle‐age, and elderly), we show successful in vitro generation of the desired levels of CML and show that they mimic those observed in vivo in several bone disorders. Formation of such physiologically relevant CML levels was achieved by selecting two oxidative/carbonyl stress compounds naturally produced in the human body, glyoxal and glyoxylic acid. Kinetic studies using the two compounds revealed differences not only between their reaction rates but also in the progression and enhanced formation of CML over other AGEs (measured by their collective fluorescence as fluorescent AGEs [fAGEs]) Consequently, through the regulation of reaction time, the levels of CML and fAGEs could be controlled and separated. Given that the developed approach does not fully eliminate the formation of other uncharacterized glycation products, this could be considered as the study limitation. We expect that the concepts of our experimental approach can be used to develop diverse strategies facilitating production of the desired levels of selected AGEs in bone and other tissues, and thus, opens new avenues for investigating the role and mechanistic aspects of specific AGEs, here CML, in bone. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.Grażyna E. SrogaDeepak VashishthWileyarticleBONE MATRIXCARBOXYMETHYLLYSINEDESIGNED IN VITRO GLYCATIONHUMANOXIDATIVE/CARBONYL STRESSOrthopedic surgeryRD701-811Diseases of the musculoskeletal systemRC925-935ENJBMR Plus, Vol 5, Iss 11, Pp n/a-n/a (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	BONE MATRIX CARBOXYMETHYLLYSINE DESIGNED IN VITRO GLYCATION HUMAN OXIDATIVE/CARBONYL STRESS Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935
spellingShingle	BONE MATRIX CARBOXYMETHYLLYSINE DESIGNED IN VITRO GLYCATION HUMAN OXIDATIVE/CARBONYL STRESS Orthopedic surgery RD701-811 Diseases of the musculoskeletal system RC925-935 Grażyna E. Sroga Deepak Vashishth Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction
description	ABSTRACT It has been a challenge to establish a link between specific advanced glycation end products (AGEs) as causal agents of different pathologies and age‐related diseases, primarily because of the lack of suitable in vitro experimental strategies facilitating increased formation of a specific AGE, here carboxymethyllysine (CML), over other AGEs under controlled conditions. CML is of considerable importance to various oxidative stress–related diseases, because in vivo formation of this AGE is connected with cellular oxidative/carbonyl metabolism. The mechanistic implications of CML accumulation in bone remain to be elucidated. To facilitate such studies, we developed a new in vitro strategy that allows preferential generation of CML in bone matrix over other AGEs. Using bone samples from human donors of different age (young, middle‐age, and elderly), we show successful in vitro generation of the desired levels of CML and show that they mimic those observed in vivo in several bone disorders. Formation of such physiologically relevant CML levels was achieved by selecting two oxidative/carbonyl stress compounds naturally produced in the human body, glyoxal and glyoxylic acid. Kinetic studies using the two compounds revealed differences not only between their reaction rates but also in the progression and enhanced formation of CML over other AGEs (measured by their collective fluorescence as fluorescent AGEs [fAGEs]) Consequently, through the regulation of reaction time, the levels of CML and fAGEs could be controlled and separated. Given that the developed approach does not fully eliminate the formation of other uncharacterized glycation products, this could be considered as the study limitation. We expect that the concepts of our experimental approach can be used to develop diverse strategies facilitating production of the desired levels of selected AGEs in bone and other tissues, and thus, opens new avenues for investigating the role and mechanistic aspects of specific AGEs, here CML, in bone. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
format	article
author	Grażyna E. Sroga Deepak Vashishth
author_facet	Grażyna E. Sroga Deepak Vashishth
author_sort	Grażyna E. Sroga
title	Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction
title_short	Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction
title_full	Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction
title_fullStr	Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction
title_full_unstemmed	Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction
title_sort	controlled formation of carboxymethyllysine in bone matrix through designed glycation reaction
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/d08c99eedae841db8cb94346a00ca5cc
work_keys_str_mv	AT grazynaesroga controlledformationofcarboxymethyllysineinbonematrixthroughdesignedglycationreaction AT deepakvashishth controlledformationofcarboxymethyllysineinbonematrixthroughdesignedglycationreaction
_version_	1718444929594687488

Controlled Formation of Carboxymethyllysine in Bone Matrix through Designed Glycation Reaction

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