PMID- 19008124
OWN - NLM
STAT- MEDLINE
DCOM- 20100114
LR  - 20161018
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 17
IP  - 4
DP  - 2009 Apr
TI  - The identification of differentially expressed microRNA in osteoarthritic tissue 
      that modulate the production of TNF-alpha and MMP13.
PG  - 464-72
LID - 10.1016/j.joca.2008.09.012 [doi]
AB  - OBJECTIVE: To identify differentially expressed microRNAs (miRNAs) in human 
      osteoarthritic (OA) cartilage and bone tissue and to determine their relevance to 
      chondrocyte function. METHODS: Cartilage and bone was obtained from OA patients 
      who underwent total knee joint replacement surgery or from post-mortem patients 
      with no previous history of OA. MiRNA expression was quantified by real-time PCR 
      (RT-PCR). Functional pathway analysis of miRNA was performed using Ingenuity 
      Pathway Analysis. Primary chondrocytes were isolated by collagenase digestion and 
      transfected with miRNA mimics and miRNA inhibitors using cationic lipid. Tumour 
      Necrosis Factor-alpha (TNF-alpha) and Matrix metalloprotease 13 (MMP13) protein 
      levels were measured by Enzyme-Linked ImmunoSorbent Assay (ELISA). RESULTS: In 
      total we identified 17 miRNA that showed greater than 4-fold differential 
      expression between OA and normal cartilage, and 30 miRNA that showed greater than 
      4-fold differential expression in OA bone. Functional pathway analysis of the 
      predicted gene targets for miR-9, miR-98, which were upregulated in both OA bone 
      and cartilage tissue, and miR-146, which was downregulated in OA cartilage, 
      suggested that these miRNA mediate inflammatory functions and pathways. 
      Over-expression of miR-9, miR-98 or miR-146 in isolated human chondrocytes 
      reduced interleukin-1 beta (IL-1 beta) induced TNF-alpha production. Furthermore, 
      inhibition and over-expression of miR-9 modulated MMP13 secretion. CONCLUSIONS: 
      We have identified a number of differentially expressed miRNAs in late-stage 
      human OA cartilage and bone. Functional analysis of miR-9, miR-98 and miR-146 in 
      primary chondrocytes suggests a role in mediating the IL-1 beta induced 
      production of TNF-alpha. MiR-9, upregulated in OA tissue, was found to inhibit 
      secretion of the collagen type II-targeting metalloproteinase MMP13 in isolated 
      human chondrocytes.
FAU - Jones, S W
AU  - Jones SW
AD  - Disease Science, Respiratory and Inflammation Research Area, AstraZeneca Alderley 
      Park, Macclesfield SK10 4TG, United Kingdom. simon.w.jones@astrazeneca.com
FAU - Watkins, G
AU  - Watkins G
FAU - Le Good, N
AU  - Le Good N
FAU - Roberts, S
AU  - Roberts S
FAU - Murphy, C L
AU  - Murphy CL
FAU - Brockbank, S M V
AU  - Brockbank SM
FAU - Needham, M R C
AU  - Needham MR
FAU - Read, S J
AU  - Read SJ
FAU - Newham, P
AU  - Newham P
LA  - eng
PT  - Journal Article
DEP - 20081011
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Inflammation Mediators)
RN  - 0 (MicroRNAs)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 3.4.24.- (MMP13 protein, human)
RN  - EC 3.4.24.- (Matrix Metalloproteinase 13)
SB  - IM
MH  - Aged
MH  - Cartilage, Articular/metabolism/pathology
MH  - Cells, Cultured
MH  - Chondrocytes/metabolism
MH  - Computational Biology/methods
MH  - Gene Expression Profiling/methods
MH  - Gene Expression Regulation
MH  - Humans
MH  - Inflammation Mediators/physiology
MH  - Matrix Metalloproteinase 13/*biosynthesis
MH  - MicroRNAs/genetics/*physiology
MH  - Middle Aged
MH  - Osteoarthritis, Knee/*genetics/metabolism/pathology
MH  - Signal Transduction/genetics/physiology
MH  - Tumor Necrosis Factor-alpha/*biosynthesis
EDAT- 2008/11/15 09:00
MHDA- 2010/01/15 06:00
CRDT- 2008/11/15 09:00
PHST- 2008/05/13 00:00 [received]
PHST- 2008/09/25 00:00 [accepted]
PHST- 2008/11/15 09:00 [pubmed]
PHST- 2010/01/15 06:00 [medline]
PHST- 2008/11/15 09:00 [entrez]
AID - S1063-4584(08)00310-5 [pii]
AID - 10.1016/j.joca.2008.09.012 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2009 Apr;17(4):464-72. doi: 10.1016/j.joca.2008.09.012. 
      Epub 2008 Oct 11.