Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Obesity is a risk factor for osteoarthritis (OA). To investigate the roles of increased mechanical loading in the onset of obesity-induced OA, knee joints were histologically analyzed after applying a tail suspension (TS) model to a high-fat diet (HFD)-induced OA model. Mice were divided into four groups: normal diet (ND) with normal loading (NL) group; HFD with NL group; ND with TS group; and HFD with TS group. Whole knee joints were evaluated by immunohistological analysis. The infrapatellar fat pad (IPFP) was excised and mRNA expression profiles were compared by qPCR analysis. After twelve weeks of the diet, body weight was increased by HFD in both the NL group and TS group. Upon histological analysis, the irregularity of the surface layer of articular cartilage was observed only in the NL+HFD group. Osteophyte area increased as a result of HFD in both the NL and TS groups, although osteophyte area in the TS+HFD group was smaller than that of the NL+HFD group. In the evaluation of the IPFP by qPCR, adipokines and inflammatory cytokines also increased as a result of HFD. While TGF-β increased as a result of HFD, the trend was slightly lower in the TS group, in parallel with osteophyte area. To detect apoptosis of articular chondrocytes, TUNEL staining was employed. TUNEL-positive cells were abundantly observed in the articular cartilage in the HFD mice regardless of mechanical loading. IPFP inflammation, enhanced chondrocyte apoptosis, and osteophyte formation were seen even in the TS group as a result of a HFD. In all, these data demonstrate that HFD contributed to osteophyte formation through mechanical loading dependent and independent mechanisms.

Related collections

Most cited references 33

Record: found
Abstract: found
Article: not found

Osteoarthritis development in novel experimental mouse models induced by knee joint instability.

Hiroshi Kawaguchi, H Chikuda, T Shimoaka … (2005)

Although osteoarthritis (OA) is induced by accumulated mechanical stress to joints, little is known about the underlying molecular mechanism. To apply approaches from mouse genomics, this study created experimental mouse OA models by producing instability in the knee joints. The models were of four types: severe, moderate, mild, and medial, depending on the severity and direction of instability imposed by combinations of ligament transection and menisectomy. OA development was evaluated by X-ray and histology by Safranin-O staining, and quantified using our original gradings. Expressions of type II, IX and X collagens and matrix metalloproteinase (MMP)-2, -3, -9 and -13 were further examined by immunohistochemistry and in situ hybridization (ISH). The severe, moderate and mild models exhibited OA development in the posterior tibial cartilage. The severe model showed cartilage destruction at 2 weeks and osteophyte formation at 4-8 weeks after surgery; however, the mild model showed only a partial cartilage destruction at 8 weeks. The grading confirmed that the OA disorders progressed depending on the severity of joint instability. In the medial model, the OA development in the medial tibial cartilage was similar to that in the posterior cartilage of the mild model. Among the collagens and MMPs, type X collagen and MMP-13 were markedly induced and colocalized in the early stage OA cartilage. We established four types of mouse models exhibiting various speeds of OA progression. By applying a mouse genomics approach to the models, molecular backgrounds in various stages of OA development can be clarified.

0 comments Cited 186 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review.

S. Clockaerts, Y.M. Bastiaansen-Jenniskens, J Runhaar … (2010)

Osteoarthritis (OA) of the knee joint is caused by genetic and hormonal factors and by inflammation, in combination with biomechanical alterations. It is characterized by loss of articular cartilage, synovial inflammation and subchondral bone sclerosis. Considerable evidence indicates that the menisci, ligaments, periarticular muscles and the joint capsule are also involved in the OA process. This paper will outline the theoretical framework for investigating the infrapatellar fat pad (IPFP) as an additional joint tissue involved in the development and progression of knee-OA. A literature search was performed in Pubmed from 1948 until October 2009 with keywords InFrapatellar fat pad, Hoffa fat pad, intraarticular adipose tissue, knee, cartilage, bone, cytokine, adipokine, inflammation, growth factor, arthritis, and OA. The IPFP is situated intracapsularly and extrasynovially in the knee joint. Besides adipocytes, the IPFP from patients with knee-OA contains macrophages, lymphocytes and granulocytes, which are able to contribute to the disease process of knee-OA. Furthermore, the IPFP contains nociceptive nerve fibers that could in part be responsible for anterior pain in knee-OA. These nerve fibers secrete substance P, which is able to induce inflammatory responses and cause vasodilation, which may lead to IPFP edema and extravasation of the immune cells. The IPFP secretes cytokines, interleukins, growth factors and adipokines that influence cartilage by upregulating the production of matrix metalloproteinases (MMPs), stimulating the expression of pro-inflammatory cytokines and inhibiting the production of cartilage matrix proteins. They may also stimulate the production of pro-inflammatory mediators, growth factors and MMPs in synovium. These data are consistent with the hypothesis that the IPFP is an osteoarthritic joint tissue capable of modulating inflammatory and destructive responses in knee-OA. Copyright 2010 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

0 comments Cited 133 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Evidence for a key role of leptin in osteoarthritis.

Hélène Dumond, Nathalie Presle, Bernard Terlain … (2003)

To evaluate the contribution of leptin (an adipose tissue-derived hormone) to the pathophysiology of osteoarthritis (OA), by determining the level of leptin in both synovial fluid (SF) and cartilage specimens obtained from human joints. We also investigated the effect of leptin on cartilage, using intraarticular injections of leptin in rats. Leptin levels in SF samples obtained from OA patients undergoing either knee replacement surgery or knee arthroscopy were measured by enzyme-linked immunosorbent assay. In addition, histologic sections of articular cartilage and osteophytes obtained during surgery for total knee replacement were graded using the Mankin score, and were immunostained using antibodies to leptin, transforming growth factor beta (TGFbeta), and insulin-like growth factor 1 (IGF-1). For experimental studies, various doses of leptin (10, 30, 100, and 300 microg) were injected into the knee joints of rats. Tibial plateaus were collected and processed for proteoglycan synthesis by radiolabeled sulfate incorporation, and for expression of leptin, its receptor (Ob-Rb), and growth factors by reverse transcriptase-polymerase chain reaction and immunohistochemical analysis. Leptin was observed in SF obtained from human OA-affected joints, and leptin concentrations correlated with the body mass index. Marked expression of the protein was observed in OA cartilage and in osteophytes, while in normal cartilage, few chondrocytes produced leptin. Furthermore, the pattern and level of leptin expression were related to the grade of cartilage destruction and paralleled those of growth factors (IGF-1 and TGFbeta1). Animal studies showed that leptin strongly stimulated anabolic functions of chondrocytes and induced the synthesis of IGF-1 and TGFbeta1 in cartilage at both the messenger RNA and the protein levels. These findings suggest a new peripheral function of leptin as a key regulator of chondrocyte metabolism, and indicate that leptin may play an important role in the pathophysiology of OA.

0 comments Cited 117 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Luc Malaval: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 9 September 2016

Publication date Collection: 2016

Volume: 11

Issue: 9

Electronic Location Identifier: e0162794

Affiliations

[1 ]Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan

[2 ]Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Sakaiminamicho Musashino-shi, Tokyo, 180-8602, Japan

[3 ]Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan

[4 ]Department of Rehabilitation Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan

Universite de Lyon, FRANCE

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Conceptualization: YA.
Data curation: YA AO YH.
Formal analysis: AO MI.
Funding acquisition: YA AO YH.
Investigation: MI HO MA ZA JP GJ YA.
Methodology: YA HO.
Project administration: YA.
Resources: YH AO.
Software: MI.
Supervision: YA AO.
Validation: MA ZA.
Visualization: YA MI.
Writing – original draft: YA.
Writing – review & editing: YA.

* E-mail: aso.orth@ 123456tmd.ac.jp

Article

Publisher ID: PONE-D-15-55397

DOI: 10.1371/journal.pone.0162794

PMC ID: 5017734

PubMed ID: 27611831

SO-VID: bb6fd60e-ddb1-4956-aaa5-b7b15ee4a138

License:

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.

History

Date received : 11 January 2016

Date accepted : 29 August 2016

Page count

Figures: 6, Tables: 0, Pages: 14

Funding

Funded by: grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan

Award ID: 24592257

Award Recipient : Yoshinori Asou

This work was supported by a grant from the Ministry of Education, Culture, Sports, Science, and Technology, Japan. The supporter had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist.

Custom metadata

Data Availability All relevant data are within the paper and its Supporting Information files.

Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis

Read this article at

Abstract

Related collections

PLOS Climate

Most cited references 33

Osteoarthritis development in novel experimental mouse models induced by knee joint instability.

The infrapatellar fat pad should be considered as an active osteoarthritic joint tissue: a narrative review.

Evidence for a key role of leptin in osteoarthritis.

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 287

Cited by 8

Most referenced authors 500