title: Initial responses of articular tissues in a murine high-fat diet-induced osteoarthritis model: pivotal role of the IPFP as a cytokine fountain.
abstract: Obesity and high body mass index are associated with a higher incidence of osteoarthritis (OA). The aim of this study is to investigate the involvement of the infrapatellar fat pad (IPFP) in the sub-acute effect of a high fat diet (HFD) on the development of knee-OA. C57BL/6J male mice were fed either a HFD or a normal diet beginning at seven weeks of age. Tissue sections were evaluated with immunohistological analysis. The IPFP was excised, and mRNA expression profiles were compared using real-time RT-PCR analysis. Osteoarthritic changes were initiated in the HFD group after eight weeks of the HFD. Increased synovial cell number and angiogenesis at the anterior edge of the tibial plateau were exhibited prior to osteophyte formation. Quantitative histological analysis indicated that osteophyte volume was significantly increased in the HFD group after eight weeks, along with an increase in the IPFP volume, the size of individual adipocytes and the number of vessels in the IPFP. Histomorphometrical analysis revealed osteophyte area was significantly associated with IPFP area, individual adipocyte area and vascular area. Real-time RT-PCR analysis demonstrated elevated mRNA expression of inflammatory cytokines, growth factor, and adipokines in the IPFP after eight weeks of the HFD. These findings are in parallel with increased expression of the CD68 macrophage marker after eight weeks of the HFD. Expression levels of the adipokines were significantly correlated with expression of TNF-α, VEGF and TGF-β. Immunohistological analysis revealed that the Nampt protein was highly expressed in the IPFP especially around the site of osteophyte formation. Apoptosis and proliferation of chondrocytes were both enhanced at the site of osteophyte formation, indicating higher cell turnover at this region. These observations suggest the IPFP plays a pivotal role in the formation of osteophytes and functions as a secretory organ in response to a HFD.
authors.affiliation: Division of Veterinary Surgery, School of Veterinary Medicine, Nippon Veterinary and Life Science University, Musashino-shi, Tokyo Japan.
authors.forename: Munetaka
authors.initials: M
authors.lastname: Iwata
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ochi
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Hara
authors.forename: Masahiro
authors.initials: M
authors.lastname: Tagawa
authors.forename: Daisuke
authors.initials: D
authors.lastname: Koga
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okawa
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Asou
mesh_terms: D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology*; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D017209:Apoptosis; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D018836:Inflammation Mediators / Q000378:metabolism; D007719:Knee Joint / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010003:Osteoarthritis / Q000378:metabolism* / Q000473:pathology*; D010329:Patella / Q000378:metabolism* / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D054392:Adipokines; D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D016207:Cytokines; D018836:Inflammation Mediators; D012333:RNA, Messenger; C067980:CD68 antigen, human; D000097382:CD68 Molecule