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Is Synovial Macrophage Activation the Inflammatory Link Between Obesity and Osteoarthritis?

  • Osteoarthritis (FJ Blanco, Guest Section Editor)
  • Published:
Current Rheumatology Reports Aims and scope Submit manuscript

Abstract

Osteoarthritis (OA) is the most common musculoskeletal disease, affecting nearly 25 % of the world population (WHO reports), leading to pain and disability. There are as yet no clinically proven therapies to halt OA onset or progression; the development of such therapies is, therefore, a national as well as international research priority. Obesity-related metabolic syndrome has been identified as the most significant, but also an entirely preventable risk factor for OA; however, the mechanisms underlying this link remain unclear. We have examined the available literature linking OA and metabolic syndrome. The two conditions have a shared pathogenesis in which chronic low-grade inflammation of affected tissues is recognized as a major factor that is associated with systemic inflammation. In addition, the occurrence of metabolic syndrome appears to alter systemic and local pro-inflammatory cytokines that are also related to the development of OA-like pathologies. Recent findings highlight the importance not only of the elevated number of macrophage in inflamed synovium but also the activation and amplification of the inflammatory state and other pathological changes. The role of local inflammation on the synovium is now considered to be a pharmacological target against which to aim disease-modifying drugs. In this review, we evaluate evidence linking OA, synovitis and metabolic syndrome and discuss the merits of targeting macrophage activation as a valid treatment option for OA.

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Abbreviations

3D:

Three dimensional

ACC:

Articular chondrocytes

ADAMTS:

A disintegrin and metalloproteinase with thrombospondin motifs

AGEs:

Advanced glycation end products

cDNA:

Complementary deoxyribonucleic acid

COL-2A:

Collagen type II

COL10-A:

Collagen type X

COX-2:

Cyclooxygenase-2

ECM:

Extracellular matrix

FACS:

Fluorescence-activated cell sorting

GAG:

Glycosaminoglycan

IGF-1:

Insulin-like growth factor-1

IL:

Interleukin

LTs:

Leukotrienes

LTA4 :

Leukotriene A4

LTB4:

Leukotriene B4

Ltb4r1 (BLT1):

High-affinity LTB4 receptor 1

MetS:

Metabolic syndrome

MMP:

Matrix metalloproteinase

mRNA:

Messenger ribonucleic acid

NDAIDs:

Non-steroidal anti-inflammatory drugs

NF-kB:

Nuclear factor kappa-light-chain-enhancer

NO:

Nitric oxide

OA:

Osteoarthritis

PD:

Protectin

RA:

Rheumatoid arthritis

ROS:

Reactive oxygen species

RAGE:

Receptors for AGE

RvD:

D-series resolvin

RvE:

E-series resolvin

RUNX:

Runt-related transcription factor

SOX:

SRY-related HMG-box

TGF:

Transforming growth factor

VEGF:

Vascular endothelial growth factor

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    1. Institute of Health and Biomedical Innovation, Queensland University of Technology, 60 Musk Ave., Kelvin Grove, QLD, 4059, Australia

      Antonia RuJia Sun, Thor Friis, Sunderajhan Sekar, Ross Crawford, Yin Xiao & Indira Prasadam

    2. Department of Orthopedics, Prince Charles Hospital, Chermside, QLD, 4032, Australia

      Ross Crawford

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    1. Antonia RuJia Sun
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    This article is part of the Topical Collection on Osteoarthritis

    Antonia RuJia Sun and Thor Friis contributed equally to this work.

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    Sun, A.R., Friis, T., Sekar, S. et al. Is Synovial Macrophage Activation the Inflammatory Link Between Obesity and Osteoarthritis?. Curr Rheumatol Rep 18, 57 (2016). https://doi.org/10.1007/s11926-016-0605-9

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