Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis

Sun, Antonia RuJia and Panchal, Sunil K. and Friis, Thor and Sekar, Sunderajhan and Crawford, Ross and Brown, Lindsay and Xiao, Yin and Prasadam, Indira (2017) Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis. PLoS One, 12 (8). pp. 1-22.

[img]
Preview
Text (Published Version)
PLoS One bone.pdf
Available under License Creative Commons Attribution 4.0.

Download (2425Kb) | Preview

Abstract

Objectives
Epidemiological and experimental studies have established obesity to be an important risk factor for osteoarthritis (OA), however, the mechanisms underlying this link remains largely unknown. Here, we studied local inflammatory responses in metabolic-OA.

Methods
Wistar rats were fed with control diet (CD) and high-carbohydrate, high-fat diet (HCHF) for period of 8 and 16 weeks. After euthanasia, the knees were examined to assess the articular cartilage changes and inflammation in synovial membrane. Further IHC was conducted to determine the macrophage-polarization status of the synovium. In addition, CD and HCHF synovial fluid was co-cultured with bone marrow-derived macrophages to assess the effect of synovial fluid inflammation on macrophage polarisation.

Results
Our study showed that, obesity induced by a high-carbohydrate, high-fat (HCHF) diet is associated with spontaneous and local inflammation of the synovial membranes in rats even before the cartilage degradation. This was followed by increased synovitis and increased macrophage infiltration into the synovium and a predominant elevation of proinflammatory M1 macrophages. In addition, bone marrow derived macrophages, cultured with synovial fluid collected from the knees of obese rats exhibited a pro-inflammatory M1 macrophage phenotype.

Conclusion
Our study demonstrate a strong association between obesity and a dynamic immune response locally within synovial tissues. Furthermore, we have also identified synovial resident macrophages to play a vital role in the inflammation caused by the HCHF diet. Therefore, future therapeutic strategies targeted at the synovial macrophage phenotype may be the key to break the link between obesity and OA.


Statistics for USQ ePrint 34071
Statistics for this ePrint Item
Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Copyright: © 2017 Sun et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Faculty / Department / School: Current - Institute for Agriculture and the Environment
Date Deposited: 09 May 2018 04:34
Last Modified: 10 May 2018 02:39
Uncontrolled Keywords: osteoarthritis, macrophages, synovium, inflammation, obesity, diet, cartilage
Fields of Research : 11 Medical and Health Sciences > 1111 Nutrition and Dietetics > 111103 Nutritional Physiology
11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111501 Basic Pharmacology
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1371/journal.pone.0183693
URI: http://eprints.usq.edu.au/id/eprint/34071

Actions (login required)

View Item Archive Repository Staff Only