PMID- 25693634
OWN - NLM
STAT- MEDLINE
DCOM- 20150811
LR  - 20181113
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 180
IP  - 3
DP  - 2015 Jun
TI  - CD11c(+) macrophages and levels of TNF-alpha and MMP-3 are increased in synovial and 
      adipose tissues of osteoarthritic mice with hyperlipidaemia.
PG  - 551-9
LID - 10.1111/cei.12607 [doi]
AB  - 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)-alpha, 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-alpha in CD11c(+) cells, which were isolated by magnetic beads, was compared to 
      CD11c(-) cells. In addition, the effect of TNF-alpha 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-alpha. Expression of TNF-alpha and MMP3 was increased in ST and AT, and was 
      decreased upon macrophage depletion. TNF-alpha 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-alpha. Our findings suggest that increased numbers of CD11c(+) macrophages and 
      elevated levels of TNF-alpha and MMP-3 in AT and ST may explain the relationship 
      between hyperlipidaemia and OA.
CI  - (c) 2015 British Society for Immunology.
FAU - Uchida, K
AU  - Uchida K
AD  - Department of Orthopedic Surgery, Kitasato University School of Medicine, 
      Sagamihara City, Kanagawa, Japan.
FAU - Satoh, M
AU  - Satoh M
AD  - Department of Immunology, Kitasato University School of Medicine, Sagamihara 
      City, Kanagawa, Japan.
FAU - Inoue, G
AU  - Inoue G
AD  - Department of Orthopedic Surgery, Kitasato University School of Medicine, 
      Sagamihara City, Kanagawa, Japan.
FAU - Onuma, K
AU  - Onuma K
AD  - Department of Orthopedic Surgery, Kitasato University School of Medicine, 
      Sagamihara City, Kanagawa, Japan.
FAU - Miyagi, M
AU  - Miyagi M
AD  - Department of Orthopedic Surgery, Kitasato University School of Medicine, 
      Sagamihara City, Kanagawa, Japan.
FAU - Iwabuchi, K
AU  - Iwabuchi K
AD  - Department of Immunology, Kitasato University School of Medicine, Sagamihara 
      City, Kanagawa, Japan.
FAU - Takaso, M
AU  - Takaso M
AD  - Department of Orthopedic Surgery, Kitasato University School of Medicine, 
      Sagamihara City, Kanagawa, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150420
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (CD11c Antigen)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.14 (Procollagen N-Endopeptidase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.82 (ADAMTS4 Protein)
RN  - EC 3.4.24.82 (Adamts4 protein, mouse)
SB  - IM
MH  - ADAM Proteins/genetics/metabolism
MH  - ADAMTS4 Protein
MH  - Adipose Tissue/*metabolism
MH  - Animals
MH  - CD11c Antigen/genetics/*metabolism
MH  - Disease Models, Animal
MH  - Fibroblasts/metabolism
MH  - Gene Expression
MH  - Hyperlipidemias/complications
MH  - Macrophages/immunology/*metabolism
MH  - Male
MH  - Matrix Metalloproteinase 3/genetics/*metabolism
MH  - Mice
MH  - Osteoarthritis/complications/genetics/*metabolism
MH  - Procollagen N-Endopeptidase/genetics/metabolism
MH  - Synovial Membrane/cytology/*metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
PMC - PMC4449783
OTO - NOTNLM
OT  - hyperlipidaemia
OT  - macrophage
OT  - matrix metalloprotease-3
OT  - osteoarthritis
OT  - tumour necrosis factor-alpha
EDAT- 2015/02/20 06:00
MHDA- 2015/08/12 06:00
PMCR- 2016/06/01
CRDT- 2015/02/20 06:00
PHST- 2015/02/12 00:00 [accepted]
PHST- 2015/02/20 06:00 [entrez]
PHST- 2015/02/20 06:00 [pubmed]
PHST- 2015/08/12 06:00 [medline]
PHST- 2016/06/01 00:00 [pmc-release]
AID - 10.1111/cei.12607 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2015 Jun;180(3):551-9. doi: 10.1111/cei.12607. Epub 2015 Apr 
      20.