title: CD11c(+) macrophages and levels of TNF-α and MMP-3 are increased in synovial and adipose tissues of osteoarthritic mice with hyperlipidaemia.
abstract: To understand more clearly the link between osteoarthritis and hyperlipidaemia, we investigated the inflammatory macrophage subsets and macrophage-regulated matrix metalloprotease-3 (MMP-3) and A disintegrin and metalloprotease with thrombospondin motifs-4 (ADAMTS4) in synovial (ST) and adipose tissues (AT) of osteoarthritic mice with hyperlipidaemia (STR/Ort). CD11c(+) F4/80(+) CD11b(+) macrophage populations in the ST and AT of 9-month-old STR/Ort and C57BL/6J mice were characterized and compared by flow cytometry and real-time polymerase chain reaction (PCR) analyses. Expression of tumour necrosis factor (TNF)-α, MMP-3 and ADAMTS4, and the response of these factors to anionic liposomal clodronate induced-macrophage depletion were also evaluated by real-time PCR. Expression of TNF-α in CD11c(+) cells, which were isolated by magnetic beads, was compared to CD11c(-) cells. In addition, the effect of TNF-α on cultured synovial fibroblasts and adipocytes was investigated. CD11c(+) F4/80(+) CD11b(+) macrophages were increased in ST and AT of STR/Ort mice. The CD11c(+) cell fraction highly expressed TNF-α. Expression of TNF-α and MMP3 was increased in ST and AT, and was decreased upon macrophage depletion. TNF-α treatment of cultured synovial fibroblasts and adipocytes markedly up-regulated MMP-3. CD11c(+) F4/80(+) CD11b(+) macrophages were identified as a common inflammatory subset in the AT and ST of STR/Ort mice with hyperlipidaemia. The induction of inflammation in AT and ST may be part of a common mechanism that regulates MMP3 expression through TNF-α. Our findings suggest that increased numbers of CD11c(+) macrophages and elevated levels of TNF-α and MMP-3 in AT and ST may explain the relationship between hyperlipidaemia and OA.
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Uchida
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Satoh
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan.
authors.forename: G
authors.initials: G
authors.lastname: Inoue
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Onuma
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Miyagi
authors.affiliation: Department of Immunology, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara City, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Takaso
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000071121:ADAMTS4 Protein; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D039521:CD11c Antigen / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D015870:Gene Expression; D006949:Hyperlipidemias / Q000150:complications; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010003:Osteoarthritis / Q000150:complications / Q000235:genetics / Q000378:metabolism*; D011348:Procollagen N-Endopeptidase / Q000235:genetics / Q000378:metabolism; D013583:Synovial Membrane / Q000166:cytology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
chemical_list: D039521:CD11c Antigen; D014409:Tumor Necrosis Factor-alpha; D051722:ADAM Proteins; D011348:Procollagen N-Endopeptidase; D019278:Matrix Metalloproteinase 3; D000071121:ADAMTS4 Protein; C000603919:Adamts4 protein, mouse
keywords: hyperlipidaemia; macrophage; matrix metalloprotease-3; osteoarthritis; tumour necrosis factor-α