The burden of metabolic syndrome on osteoarthritic joints

Bruce M Dickson, Anke J Roelofs, Justin J Rochford, Heather M Wilson, Cosimo de Bari* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

Background
The prevalence of osteoarthritis (OA) increases with obesity, with up to two thirds of the elderly obese population affected by OA of the knee. The metabolic syndrome (MetS), frequently associated with central obesity and characterised by elevated waist circumference, raised fasting plasma glucose concentration, raised triglycerides, reduced high-density lipoproteins, and/or hypertension, is implicated in the pathogenesis of OA. This narrative review discusses the mechanisms involved in the influence of MetS on OA, with a focus on the effects on macrophages and chondrocytes.

Main text
A skewing of macrophages towards a pro-inflammatory M1 phenotype within synovial and adipose tissues is thought to play a role in OA pathogenesis. The metabolic perturbations typical of MetS are important drivers of pro-inflammatory macrophage polarisation and activity. This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5′ adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. Altered levels of adipokines, including leptin and adiponectin, further influence macrophage polarisation. The metabolic alterations in MetS also affect the cartilage through direct effects on chondrocytes by stimulating the production of pro-inflammatory and catabolic factors and possibly by suppressing autophagy and promoting cellular senescence.

Conclusions
The influence of MetS on OA pathogenesis involves a wide range of metabolic alterations that directly affect macrophages and chondrocytes. The relative burden of intra-articular versus systemic adipose tissue in the MetS-associated OA remains to be clarified. Understanding how altered metabolism interacts with joints affected by OA is crucial for the development of further strategies for treating this debilitating condition, such as supplementing existing therapies with metformin and utilising ω-3 fatty acid derivatives to restore imbalances in ω-3 and ω-6 fatty acids.
Original languageEnglish
Article number289
JournalArthritis Research & Therapy
Volume21
DOIs
Publication statusPublished - 16 Dec 2019

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Osteoarthritis
Joints
Macrophages
Chondrocytes
Adipose Tissue
Fatty Acids
Advanced Glycosylation End Products
Adipokines
Abdominal Obesity
Knee Osteoarthritis
Cell Aging
Metformin
Adiponectin
Autophagy
Waist Circumference
Succinic Acid
Adenosine Monophosphate
HDL Lipoproteins
Leptin
Nonesterified Fatty Acids

Keywords

  • osteoarthritis
  • metabolic syndrome
  • obesity
  • macrophage
  • chondrocyte

Cite this

@article{058c66bb1abd4776b948d5b2cf7aef72,
title = "The burden of metabolic syndrome on osteoarthritic joints",
abstract = "BackgroundThe prevalence of osteoarthritis (OA) increases with obesity, with up to two thirds of the elderly obese population affected by OA of the knee. The metabolic syndrome (MetS), frequently associated with central obesity and characterised by elevated waist circumference, raised fasting plasma glucose concentration, raised triglycerides, reduced high-density lipoproteins, and/or hypertension, is implicated in the pathogenesis of OA. This narrative review discusses the mechanisms involved in the influence of MetS on OA, with a focus on the effects on macrophages and chondrocytes.Main textA skewing of macrophages towards a pro-inflammatory M1 phenotype within synovial and adipose tissues is thought to play a role in OA pathogenesis. The metabolic perturbations typical of MetS are important drivers of pro-inflammatory macrophage polarisation and activity. This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5′ adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. Altered levels of adipokines, including leptin and adiponectin, further influence macrophage polarisation. The metabolic alterations in MetS also affect the cartilage through direct effects on chondrocytes by stimulating the production of pro-inflammatory and catabolic factors and possibly by suppressing autophagy and promoting cellular senescence.ConclusionsThe influence of MetS on OA pathogenesis involves a wide range of metabolic alterations that directly affect macrophages and chondrocytes. The relative burden of intra-articular versus systemic adipose tissue in the MetS-associated OA remains to be clarified. Understanding how altered metabolism interacts with joints affected by OA is crucial for the development of further strategies for treating this debilitating condition, such as supplementing existing therapies with metformin and utilising ω-3 fatty acid derivatives to restore imbalances in ω-3 and ω-6 fatty acids.",
keywords = "osteoarthritis, metabolic syndrome, obesity, macrophage, chondrocyte",
author = "Dickson, {Bruce M} and Roelofs, {Anke J} and Rochford, {Justin J} and Wilson, {Heather M} and {de Bari}, Cosimo",
note = "Versus Arthritis (grants 19667, 20050, 20775, 20865, 21156) and the Medical Research Council (grant MR/L020211/1).",
year = "2019",
month = "12",
day = "16",
doi = "10.1186/s13075-019-2081-x",
language = "English",
volume = "21",
journal = "Arthritis Research & Therapy",
issn = "1478-6354",
publisher = "BioMed Central",

}

TY - JOUR

T1 - The burden of metabolic syndrome on osteoarthritic joints

AU - Dickson, Bruce M

AU - Roelofs, Anke J

AU - Rochford, Justin J

AU - Wilson, Heather M

AU - de Bari, Cosimo

N1 - Versus Arthritis (grants 19667, 20050, 20775, 20865, 21156) and the Medical Research Council (grant MR/L020211/1).

PY - 2019/12/16

Y1 - 2019/12/16

N2 - BackgroundThe prevalence of osteoarthritis (OA) increases with obesity, with up to two thirds of the elderly obese population affected by OA of the knee. The metabolic syndrome (MetS), frequently associated with central obesity and characterised by elevated waist circumference, raised fasting plasma glucose concentration, raised triglycerides, reduced high-density lipoproteins, and/or hypertension, is implicated in the pathogenesis of OA. This narrative review discusses the mechanisms involved in the influence of MetS on OA, with a focus on the effects on macrophages and chondrocytes.Main textA skewing of macrophages towards a pro-inflammatory M1 phenotype within synovial and adipose tissues is thought to play a role in OA pathogenesis. The metabolic perturbations typical of MetS are important drivers of pro-inflammatory macrophage polarisation and activity. This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5′ adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. Altered levels of adipokines, including leptin and adiponectin, further influence macrophage polarisation. The metabolic alterations in MetS also affect the cartilage through direct effects on chondrocytes by stimulating the production of pro-inflammatory and catabolic factors and possibly by suppressing autophagy and promoting cellular senescence.ConclusionsThe influence of MetS on OA pathogenesis involves a wide range of metabolic alterations that directly affect macrophages and chondrocytes. The relative burden of intra-articular versus systemic adipose tissue in the MetS-associated OA remains to be clarified. Understanding how altered metabolism interacts with joints affected by OA is crucial for the development of further strategies for treating this debilitating condition, such as supplementing existing therapies with metformin and utilising ω-3 fatty acid derivatives to restore imbalances in ω-3 and ω-6 fatty acids.

AB - BackgroundThe prevalence of osteoarthritis (OA) increases with obesity, with up to two thirds of the elderly obese population affected by OA of the knee. The metabolic syndrome (MetS), frequently associated with central obesity and characterised by elevated waist circumference, raised fasting plasma glucose concentration, raised triglycerides, reduced high-density lipoproteins, and/or hypertension, is implicated in the pathogenesis of OA. This narrative review discusses the mechanisms involved in the influence of MetS on OA, with a focus on the effects on macrophages and chondrocytes.Main textA skewing of macrophages towards a pro-inflammatory M1 phenotype within synovial and adipose tissues is thought to play a role in OA pathogenesis. The metabolic perturbations typical of MetS are important drivers of pro-inflammatory macrophage polarisation and activity. This is mediated via alterations in the levels and activities of the cellular nutrient sensors 5′ adenosine monophosphate-activated protein kinase (AMPK) and mammalian target of rapamycin complex 1 (mTORC1), intracellular accumulation of metabolic intermediates such as succinate and citrate, and increases in free fatty acids (FFAs) and hyperglycaemia-induced advanced glycation end-products (AGEs) that bind to receptors on the macrophage surface. Altered levels of adipokines, including leptin and adiponectin, further influence macrophage polarisation. The metabolic alterations in MetS also affect the cartilage through direct effects on chondrocytes by stimulating the production of pro-inflammatory and catabolic factors and possibly by suppressing autophagy and promoting cellular senescence.ConclusionsThe influence of MetS on OA pathogenesis involves a wide range of metabolic alterations that directly affect macrophages and chondrocytes. The relative burden of intra-articular versus systemic adipose tissue in the MetS-associated OA remains to be clarified. Understanding how altered metabolism interacts with joints affected by OA is crucial for the development of further strategies for treating this debilitating condition, such as supplementing existing therapies with metformin and utilising ω-3 fatty acid derivatives to restore imbalances in ω-3 and ω-6 fatty acids.

KW - osteoarthritis

KW - metabolic syndrome

KW - obesity

KW - macrophage

KW - chondrocyte

U2 - 10.1186/s13075-019-2081-x

DO - 10.1186/s13075-019-2081-x

M3 - Article

C2 - 31842972

VL - 21

JO - Arthritis Research & Therapy

JF - Arthritis Research & Therapy

SN - 1478-6354

M1 - 289

ER -