Pleiotropic Functions of High Fat Diet in the Etiology of Osteoarthritis.
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.
Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.
Yoshinori
Y
Asou
Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Sakaiminamicho Musashino-shi, Tokyo, 180-8602, Japan.
Munetaka
M
Iwata
Department of Physiology and Cell Biology, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.
Hiroki
H
Ochi
Department of Rehabilitation Medicine, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.
Maierhaba
M
Ailixiding
Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.
Zulipiya
Z
Aibibula
Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.
Jinying
J
Piao
Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.
Guangwen
G
Jin
Division of Veterinary Surgery, Nippon Veterinary and Life Science University, 1-7-1 Sakaiminamicho Musashino-shi, Tokyo, 180-8602, Japan.
Yasushi
Y
Hara
Department of Orthopedics Surgery, Tokyo Medical and Dental University, 1-5-45 Yushima Bunkyo-ku, Tokyo, 113-8519, Japan.
Atsushi
A
Okawa
D000273:Adipose Tissue / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D001696:Biomechanical Phenomena; D001835:Body Weight; D002358:Cartilage, Articular / Q000473:pathology; D019902:Chondrocytes / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D020287:In Situ Nick-End Labeling; D035002:Lower Extremity / Q000000981:diagnostic imaging / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009929:Organ Size; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology; D054850:Osteophyte / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016474:Weight-Bearing; D055114:X-Ray Microtomography
D012333:RNA, Messenger