PMID- 19684582
OWN - NLM
STAT- MEDLINE
DCOM- 20091002
LR  - 20211020
IS  - 1546-170X (Electronic)
IS  - 1078-8956 (Linking)
VI  - 15
IP  - 9
DP  - 2009 Sep
TI  - Syndecan-4 regulates ADAMTS-5 activation and cartilage breakdown in 
      osteoarthritis.
PG  - 1072-6
LID - 10.1038/nm.1998 [doi]
AB  - Aggrecan cleavage by a disintegrin and metalloproteinase with a thrombospondin 
      type 1 motif, member 5 (ADAMTS-5) is crucial for the breakdown of cartilage 
      matrix during osteoarthritis, a degenerative joint disease that leads to the 
      progressive destruction of articular structures. The mechanisms of ADAMTS-5 
      activation and their links to the pathogenesis of osteoarthritis remain poorly 
      understood, but syndecans have been shown to be involved in the activation of 
      ADAMTS-4 (ref. 3). Here we show that syndecan-4 is specifically induced in type X 
      collagen-producing chondrocytes both in human osteoarthritis and in murine models 
      of the disease. The loss of syndecan-4 in genetically modified mice and 
      intra-articular injections of syndecan-4-specific antibodies into wild-type mice 
      protect from proteoglycan loss and thereby prevent osteoarthritic cartilage 
      damage in a surgically induced model of osteoarthritis. The occurrence of less 
      severe osteoarthritis-like cartilage destruction in both syndecan-4-deficient 
      mice and syndecan-4-specific antibody-treated wild-type mice results from a 
      marked decrease in ADAMTS-5 activity. Syndecan-4 controls the activation of 
      ADAMTS-5 through direct interaction with the protease and through regulating 
      mitogen-activated protein kinase (MAPK)-dependent synthesis of matrix 
      metalloproteinase-3 (MMP-3). Our data suggest that strategies aimed at the 
      inhibition of syndecan-4 will be of great value for the treatment of cartilage 
      damage in osteoarthritis.
FAU - Echtermeyer, Frank
AU  - Echtermeyer F
AD  - Department of Anesthesiology and Intensive Care Medicine, Medical University 
      Hannover, Hannover, Germany. echtermeyer.frank@mh-hannover.de
FAU - Bertrand, Jessica
AU  - Bertrand J
FAU - Dreier, Rita
AU  - Dreier R
FAU - Meinecke, Ingmar
AU  - Meinecke I
FAU - Neugebauer, Katja
AU  - Neugebauer K
FAU - Fuerst, Martin
AU  - Fuerst M
FAU - Lee, Yun Jong
AU  - Lee YJ
FAU - Song, Yeong Wook
AU  - Song YW
FAU - Herzog, Christine
AU  - Herzog C
FAU - Theilmeier, Gregor
AU  - Theilmeier G
FAU - Pap, Thomas
AU  - Pap T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090816
PL  - United States
TA  - Nat Med
JT  - Nature medicine
JID - 9502015
RN  - 0 (Collagen Type X)
RN  - 0 (RNA, Messenger)
RN  - 0 (SDC4 protein, human)
RN  - 0 (Sdc4 protein, mouse)
RN  - 0 (Sdc4 protein, rat)
RN  - 0 (Syndecan-4)
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.- (Adamts5 protein, mouse)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.17 (Mmp3 protein, mouse)
SB  - IM
MH  - ADAM Proteins/genetics/*physiology
MH  - ADAMTS5 Protein
MH  - Animals
MH  - Cartilage/pathology
MH  - Chondrocytes/pathology/physiology
MH  - Collagen Type X/biosynthesis
MH  - Disease Models, Animal
MH  - Humans
MH  - MAP Kinase Signaling System
MH  - Matrix Metalloproteinase 3/deficiency/genetics/physiology
MH  - Mice
MH  - Mice, Knockout
MH  - Osteoarthritis/*etiology/pathology/*physiopathology
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Syndecan-4/antagonists & inhibitors/deficiency/genetics/*physiology
EDAT- 2009/08/18 09:00
MHDA- 2009/10/03 06:00
CRDT- 2009/08/18 09:00
PHST- 2009/01/13 00:00 [received]
PHST- 2009/06/01 00:00 [accepted]
PHST- 2009/08/18 09:00 [entrez]
PHST- 2009/08/18 09:00 [pubmed]
PHST- 2009/10/03 06:00 [medline]
AID - nm.1998 [pii]
AID - 10.1038/nm.1998 [doi]
PST - ppublish
SO  - Nat Med. 2009 Sep;15(9):1072-6. doi: 10.1038/nm.1998. Epub 2009 Aug 16.