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

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 wit...

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Autores principales: Sun, Antonia RuJia, Panchal, Sunil K., Friis, Thor, Sekar, Sunderajhan, Crawford, Ross, Brown, Lindsay, Xiao, Yin, Prasadam, Indira
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578643/
https://www.ncbi.nlm.nih.gov/pubmed/28859108
http://dx.doi.org/10.1371/journal.pone.0183693
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author Sun, Antonia RuJia
Panchal, Sunil K.
Friis, Thor
Sekar, Sunderajhan
Crawford, Ross
Brown, Lindsay
Xiao, Yin
Prasadam, Indira
author_facet Sun, Antonia RuJia
Panchal, Sunil K.
Friis, Thor
Sekar, Sunderajhan
Crawford, Ross
Brown, Lindsay
Xiao, Yin
Prasadam, Indira
author_sort Sun, Antonia RuJia
collection PubMed
description 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 pro-inflammatory 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.
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spelling pubmed-55786432017-09-15 Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis Sun, Antonia RuJia Panchal, Sunil K. Friis, Thor Sekar, Sunderajhan Crawford, Ross Brown, Lindsay Xiao, Yin Prasadam, Indira PLoS One Research Article 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 pro-inflammatory 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. Public Library of Science 2017-08-31 /pmc/articles/PMC5578643/ /pubmed/28859108 http://dx.doi.org/10.1371/journal.pone.0183693 Text en © 2017 Sun et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Sun, Antonia RuJia
Panchal, Sunil K.
Friis, Thor
Sekar, Sunderajhan
Crawford, Ross
Brown, Lindsay
Xiao, Yin
Prasadam, Indira
Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis
title Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis
title_full Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis
title_fullStr Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis
title_full_unstemmed Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis
title_short Obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis
title_sort obesity-associated metabolic syndrome spontaneously induces infiltration of pro-inflammatory macrophage in synovium and promotes osteoarthritis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578643/
https://www.ncbi.nlm.nih.gov/pubmed/28859108
http://dx.doi.org/10.1371/journal.pone.0183693
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