PMID- 21917825
OWN - NLM
STAT- MEDLINE
DCOM- 20120208
LR  - 20161125
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Linking)
VI  - 71
IP  - 1
DP  - 2012 Jan
TI  - CCAAT/enhancer binding protein beta regulates expression of matrix 
      metalloproteinase-3 in arthritis.
PG  - 99-107
LID - 10.1136/annrheumdis-2011-200061 [doi]
AB  - OBJECTIVES: To investigate whether CCAAT/enhancer binding protein beta (C/EBPbeta) 
      mediates the expression of matrix metalloproteinase-3 (MMP-3) and aggrecanases in 
      arthritis. METHODS: Localisation of C/EBPbeta and MMP-3 in synovium and cartilage 
      from patients with rheumatoid arthritis and osteoarthritis was determined by 
      immunohistochemistry. Cell lines SW982, C28/I2 and human fibroblast-like 
      synoviocytes stimulated by interleukin 1beta (IL-1beta) were subjected to western 
      blotting and quantitative PCR. Overexpression of C/EBPbeta by adenovirus was 
      performed in cells and organ culture of normal cartilage. Knockdown of C/EBPbeta by 
      small interference RNA was performed in cells. Activity of the human MMP-3 and 
      aggrecanase-2 ADAMTS-5 (a disintegrin and metalloproteinase with thrombospondin 
      motifs) promoters was analysed by a luciferase assay. To determine whether C/EBPbeta 
      directly binds to the MMP-3 or ADAMTS-5 promoter,a chromatin immunoprecipitation 
      assay was performed. RESULTS: Immunohistochemistry showed that C/EBPbeta and MMP-3 
      were co-localised in arthritic synovium and cartilage. Western blots revealed 
      increased C/EBPbeta expression in cells treated with IL-1beta. Expression of MMP-3, 
      MMP-13 and ADAMTS-5 mRNA was significantly increased by the overexpression of 
      C/EBPbeta. C/EBPbeta stimulated MMP-3 expression and induced matrix degradation in 
      cartilage explants. C/EBPbeta knockdown reduced MMP-3 and ADAMTS-5 expression. 
      C/EBPbeta stimulated the 2011 bp MMP-3 promoter and the 1768 bp ADAMTS-5 promoter in 
      a dose-dependent manner. Deletion and mutation analysis of the MMP-3 promoter 
      showed that the C/EBPbeta core responsive element was located between -108 bp and 
      -100 bp. The chromatin immunoprecipitation assay showed that C/EBPbeta was directly 
      bound to MMP-3 and ADAMTS-5 promoters. CONCLUSIONS: These data demonstrate that 
      C/EBPbeta is involved in expression of MMP-3 and ADAMTS-5 in arthritic synovium and 
      cartilage.
FAU - Tsushima, Hidetoshi
AU  - Tsushima H
AD  - Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu 
      University, Fukuoka, Japan.
FAU - Okazaki, Ken
AU  - Okazaki K
FAU - Hayashida, Mitsumasa
AU  - Hayashida M
FAU - Ushijima, Takahiro
AU  - Ushijima T
FAU - Iwamoto, Yukihide
AU  - Iwamoto Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110913
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (CCAAT-Enhancer-Binding Protein-beta)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (ADAMTS5 Protein)
RN  - EC 3.4.24.- (ADAMTS5 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
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)
SB  - IM
MH  - ADAM Proteins/metabolism
MH  - ADAMTS4 Protein
MH  - ADAMTS5 Protein
MH  - Aged
MH  - Aged, 80 and over
MH  - Arthritis, Rheumatoid/*metabolism
MH  - CCAAT-Enhancer-Binding Protein-beta/genetics/metabolism/*physiology
MH  - Cartilage, Articular/enzymology/metabolism
MH  - Cell Line
MH  - Gene Expression Regulation/drug effects
MH  - Gene Expression Regulation, Enzymologic/*physiology
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Matrix Metalloproteinase 13/metabolism
MH  - Matrix Metalloproteinase 3/biosynthesis/genetics/*metabolism
MH  - Middle Aged
MH  - Osteoarthritis, Knee/*metabolism
MH  - Procollagen N-Endopeptidase/metabolism
MH  - Promoter Regions, Genetic
MH  - RNA, Messenger/genetics
MH  - RNA, Small Interfering/genetics
MH  - Synovial Membrane/metabolism
MH  - Tissue Culture Techniques
MH  - Young Adult
EDAT- 2011/09/16 06:00
MHDA- 2012/02/09 06:00
CRDT- 2011/09/16 06:00
PHST- 2011/09/16 06:00 [entrez]
PHST- 2011/09/16 06:00 [pubmed]
PHST- 2012/02/09 06:00 [medline]
AID - annrheumdis-2011-200061 [pii]
AID - 10.1136/annrheumdis-2011-200061 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2012 Jan;71(1):99-107. doi: 10.1136/annrheumdis-2011-200061. Epub 
      2011 Sep 13.