DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?

This review presents our own and literature data dedicated to predisposing and pathogenetic factors involved in development of a common comorbidity, diabetes-associated osteoarthritis (DAOA). So far, there is no wide-accepted clinical or scientific viewing of DAOA as a distinct clinical phenotype of...

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Autores principales: E. V. Kazygasheva, V. S. Shirinsky, I. V. Shirinsky
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Publicado: SPb RAACI 2016
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spelling oai:doaj.org-article:7c891acefd2f44a092f26d0461ef567c2021-11-18T08:03:45ZDIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?1563-06252313-741X10.15789/1563-0625-2016-4-317-330https://doaj.org/article/7c891acefd2f44a092f26d0461ef567c2016-08-01T00:00:00Zhttps://www.mimmun.ru/mimmun/article/view/1054https://doaj.org/toc/1563-0625https://doaj.org/toc/2313-741XThis review presents our own and literature data dedicated to predisposing and pathogenetic factors involved in development of a common comorbidity, diabetes-associated osteoarthritis (DAOA). So far, there is no wide-accepted clinical or scientific viewing of DAOA as a distinct clinical phenotype of osteoarthritis (OA). To our knowledge, the role of genetic factors in DAOA development was not discussed in details. Therefore, we have drawn attention to the cross-acting genes involved in both OA and diabetes, i.e., PPARγ, FTO, ADIPOQ, and AGE. These genes encode proteins which can contribute to the pathogenesis of both OA and diabetes. However, some controversies exist about genetic predisposal for OA and diabetes. We review the studies which concern various clinical characteristics of DAOA. We describe a role of chronic hyperglycemia, insulin resistance, advanced glycation end-products (AGE) in development of OA and micro- and macrovascular complications of diabetes. The mechanisms of low-grade inflammation, humoral and cellular immune responses to cartilage antigens, and their role in OA progression are discussed. We underline a similarity of low-grade inflammation in OA and microvascular complications in diabetes. In conclusion, OA and diabetes comorbidity is not a mere coincidence of these diseases. They share some common genetic and pathogenetic factors, a distinct phenotype, and may change thinking of physicians and scientists towards a holistic (personalized) approach to prevention, diagnosis, treatment and prognosis of this comorbidity. We discuss opportunities of DAOA pharmacotherapy based on the key comorbidity feature, i.e., emergence of a new disease property by coexistence of several diseases. One may hypothesize that studying genetic, molecular, and cellular networks in comorbidities may lead to new treatment strategies (‘network pharmacology”) based on targeting the network hubs. We provide examples of such approach in some polypathies (e.g., phenofibrate, a PPARα agonist; simvastatin, a GMGCoA reductase in OA, rheumatoid arthritis and psoriasis), and its potential discuss usefulness is discussed for DAOA. In particular, we provide an example of a pilot study of ademethionine, a methyl group donator.E. V. KazygashevaV. S. ShirinskyI. V. ShirinskySPb RAACIarticlediabetes-associated osteoarthritiscomorbiditytype 2 diabetesosteoarthritisgeneticsimmunopathogenesisImmunologic diseases. AllergyRC581-607RUMedicinskaâ Immunologiâ, Vol 18, Iss 4, Pp 317-330 (2016)
institution DOAJ
collection DOAJ
language RU
topic diabetes-associated osteoarthritis
comorbidity
type 2 diabetes
osteoarthritis
genetics
immunopathogenesis
Immunologic diseases. Allergy
RC581-607
spellingShingle diabetes-associated osteoarthritis
comorbidity
type 2 diabetes
osteoarthritis
genetics
immunopathogenesis
Immunologic diseases. Allergy
RC581-607
E. V. Kazygasheva
V. S. Shirinsky
I. V. Shirinsky
DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?
description This review presents our own and literature data dedicated to predisposing and pathogenetic factors involved in development of a common comorbidity, diabetes-associated osteoarthritis (DAOA). So far, there is no wide-accepted clinical or scientific viewing of DAOA as a distinct clinical phenotype of osteoarthritis (OA). To our knowledge, the role of genetic factors in DAOA development was not discussed in details. Therefore, we have drawn attention to the cross-acting genes involved in both OA and diabetes, i.e., PPARγ, FTO, ADIPOQ, and AGE. These genes encode proteins which can contribute to the pathogenesis of both OA and diabetes. However, some controversies exist about genetic predisposal for OA and diabetes. We review the studies which concern various clinical characteristics of DAOA. We describe a role of chronic hyperglycemia, insulin resistance, advanced glycation end-products (AGE) in development of OA and micro- and macrovascular complications of diabetes. The mechanisms of low-grade inflammation, humoral and cellular immune responses to cartilage antigens, and their role in OA progression are discussed. We underline a similarity of low-grade inflammation in OA and microvascular complications in diabetes. In conclusion, OA and diabetes comorbidity is not a mere coincidence of these diseases. They share some common genetic and pathogenetic factors, a distinct phenotype, and may change thinking of physicians and scientists towards a holistic (personalized) approach to prevention, diagnosis, treatment and prognosis of this comorbidity. We discuss opportunities of DAOA pharmacotherapy based on the key comorbidity feature, i.e., emergence of a new disease property by coexistence of several diseases. One may hypothesize that studying genetic, molecular, and cellular networks in comorbidities may lead to new treatment strategies (‘network pharmacology”) based on targeting the network hubs. We provide examples of such approach in some polypathies (e.g., phenofibrate, a PPARα agonist; simvastatin, a GMGCoA reductase in OA, rheumatoid arthritis and psoriasis), and its potential discuss usefulness is discussed for DAOA. In particular, we provide an example of a pilot study of ademethionine, a methyl group donator.
format article
author E. V. Kazygasheva
V. S. Shirinsky
I. V. Shirinsky
author_facet E. V. Kazygasheva
V. S. Shirinsky
I. V. Shirinsky
author_sort E. V. Kazygasheva
title DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?
title_short DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?
title_full DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?
title_fullStr DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?
title_full_unstemmed DIABETES-ASSOCIATED OSTEOARTHRITIS: A SYNTROPY?
title_sort diabetes-associated osteoarthritis: a syntropy?
publisher SPb RAACI
publishDate 2016
url https://doaj.org/article/7c891acefd2f44a092f26d0461ef567c
work_keys_str_mv AT evkazygasheva diabetesassociatedosteoarthritisasyntropy
AT vsshirinsky diabetesassociatedosteoarthritisasyntropy
AT ivshirinsky diabetesassociatedosteoarthritisasyntropy
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