PMID- 18662930
OWN - NLM
STAT- MEDLINE
DCOM- 20090624
LR  - 20211020
IS  - 1468-2060 (Electronic)
IS  - 0003-4967 (Print)
IS  - 0003-4967 (Linking)
VI  - 68
IP  - 6
DP  - 2009 Jun
TI  - Hyaluronan inhibits expression of ADAMTS4 (aggrecanase-1) in human osteoarthritic 
      chondrocytes.
PG  - 1051-8
LID - 10.1136/ard.2007.086884 [doi]
AB  - BACKGROUND: Intra-articular injection of hyaluronan (HA) has been suggested to 
      have a disease-modifying effect in osteoarthritis, but little is known about the 
      possible mechanisms. OBJECTIVE: To investigate the effects of HA species of 
      different molecular mass, including 800 kDa (HA800) and 2700 kDa (HA2700), on the 
      expression of aggrecanases (ie, ADAMTS species), which play a key role in 
      aggrecan degradation. METHODS: The effects of HA species on the expression of 
      ADAMTS1, 4, 5, 8, 9 and 15 in interleukin 1alpha (IL1alpha)-stimulated 
      osteoarthritic chondrocytes were studied by reverse transcription PCR and 
      real-time PCR. Expression of ADAMTS4 protein and aggrecanase activity and signal 
      transduction pathways of IL1, CD44 and intracellular adhesion molecule 1 (ICAM1) 
      were examined by immunoblotting. RESULTS: IL1alpha treatment of chondrocytes 
      induced ADAMTS4, and HA800 and HA2700 significantly decreased IL1alpha-induced 
      expression of ADAMTS4 mRNA and protein. IL1alpha-stimulated aggrecanase activity 
      in osteoarthritic chondrocytes was reduced by treatment with HA2700 or 
      transfection of small interfering RNA for ADAMTS4. A similar result was obtained 
      when HA2700 was added to explant cultures of osteoarthritic cartilage. HA2700 
      neither directly inhibited nor bound to ADAMTS4. Downregulation of ADAMTS4 
      expression by HA2700 was attenuated by treatment of IL1alpha-treated chondrocytes 
      with antibodies to CD44 and/or ICAM1. The increased phosphorylation of IL1 
      receptor-associated kinase-1 and extracellular signal-regulated protein kinase1/2 
      induced by the IL1alpha treatment was downregulated by enhanced IRAK-M expression 
      after HA2700 treatment. CONCLUSION: These data suggest that HA2700 suppresses 
      aggrecan degradation by downregulating IL1alpha-induced ADAMTS4 expression 
      through the CD44 and ICAM1 signalling pathways in osteoarthritic chondrocytes.
FAU - Yatabe, T
AU  - Yatabe T
AD  - Department of Pathology, Keio University, Tokyo, Japan.
FAU - Mochizuki, S
AU  - Mochizuki S
FAU - Takizawa, M
AU  - Takizawa M
FAU - Chijiiwa, M
AU  - Chijiiwa M
FAU - Okada, A
AU  - Okada A
FAU - Kimura, T
AU  - Kimura T
FAU - Fujita, Y
AU  - Fujita Y
FAU - Matsumoto, H
AU  - Matsumoto H
FAU - Toyama, Y
AU  - Toyama Y
FAU - Okada, Y
AU  - Okada Y
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080728
PL  - England
TA  - Ann Rheum Dis
JT  - Annals of the rheumatic diseases
JID - 0372355
RN  - 0 (Hyaluronan Receptors)
RN  - 0 (Ifna6 protein, mouse)
RN  - 0 (Interferon Type I)
RN  - 0 (Interferon-alpha)
RN  - 0 (Interleukin-1alpha)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 9004-61-9 (Hyaluronic Acid)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.14 (Procollagen N-Endopeptidase)
RN  - EC 3.4.24.82 (ADAMTS4 Protein)
RN  - EC 3.4.24.82 (ADAMTS4 protein, human)
RN  - EC 3.4.24.82 (Adamts4 protein, mouse)
SB  - IM
MH  - ADAM Proteins/analysis/genetics/*metabolism
MH  - ADAMTS4 Protein
MH  - Cartilage, Articular/*enzymology
MH  - Cells, Cultured
MH  - Chondrocytes/drug effects/*enzymology
MH  - Down-Regulation
MH  - Gene Expression/drug effects
MH  - Humans
MH  - Hyaluronan Receptors/metabolism
MH  - Hyaluronic Acid/*pharmacology/therapeutic use
MH  - Immunoblotting
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Interferon Type I
MH  - Interferon-alpha
MH  - Interleukin-1alpha/pharmacology
MH  - Matrix Metalloproteinases/metabolism
MH  - Molecular Weight
MH  - Osteoarthritis/drug therapy/*enzymology
MH  - Procollagen N-Endopeptidase/analysis/genetics/*metabolism
MH  - RNA, Messenger/analysis
MH  - RNA, Small Interfering/genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction/methods
MH  - Signal Transduction/drug effects
MH  - Statistics, Nonparametric
MH  - Transfection/methods
PMC - PMC2674548
COIS- Competing interests: None.
EDAT- 2008/07/30 09:00
MHDA- 2009/06/25 09:00
PMCR- 2009/01/05
CRDT- 2008/07/30 09:00
PHST- 2008/07/30 09:00 [pubmed]
PHST- 2009/06/25 09:00 [medline]
PHST- 2008/07/30 09:00 [entrez]
PHST- 2009/01/05 00:00 [pmc-release]
AID - ard.2007.086884 [pii]
AID - ar86884 [pii]
AID - 10.1136/ard.2007.086884 [doi]
PST - ppublish
SO  - Ann Rheum Dis. 2009 Jun;68(6):1051-8. doi: 10.1136/ard.2007.086884. Epub 2008 Jul 
      28.