Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis.

Yoshinori Asou,Guangwen Jin,Maierhaba Ailixiding,Munetaka Iwata,Zulipiya Aibibula,Hiroki Ochi,Atsushi Okawa,Yasushi Hara,Jinying Piao,Luc Malaval

doi:10.1371/journal.pone.0162794

Yoshinori Asou, Guangwen Jin + Show 8 more

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https://doi.org/10.1371/journal.pone.0162794

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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.

Highlights

Osteoarthritis (OA), a chronic degenerative joint disorder characterized by articular cartilage destruction and osteophyte formation, is a major cause of disability
tail suspension (TS)+high-fat diet (HFD) mice weighed 18% more by 8 weeks and 31% more by 12 weeks when compared with TS+normal diet (ND) mice, they weighed 20% less by 8 weeks and 18% less by 12 weeks when compared with normal loading (NL)+HFD mice
It was found that HFD induced OA changes, including proteoglycan loss, chondrocyte apoptosis, and osteophyte formation, in association with infrapatellar fat pad (IPFP) inflammation by 3 months of exposure to high fat diet in both a normal loading and tail suspension mouse model

Summary

Introduction

Osteoarthritis (OA), a chronic degenerative joint disorder characterized by articular cartilage destruction and osteophyte formation, is a major cause of disability. While mechanical factors are implicated in the cause of OA, trauma, joint instability, and developmental dysplasias are all recognized as predisposing factors and have been affirmed in animal models [6]. As these factors alter the extent of mechanical loading to the joints, OA is suggested to be induced by an increase in mechanical loading. Tail suspension is an animal model of hindlimb unloading. Skeletal unloading of F344/N rats increases alkaline phosphatase activity at the deep zone in association with a decrease in proteoglycan content in the articular cartilage [8]

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