PMID- 16646035
OWN - NLM
STAT- MEDLINE
DCOM- 20060804
LR  - 20191210
IS  - 0004-3591 (Print)
IS  - 0004-3591 (Linking)
VI  - 54
IP  - 5
DP  - 2006 May
TI  - Connective tissue growth factor/CCN2 overexpression in mouse synovial lining 
      results in transient fibrosis and cartilage damage.
PG  - 1653-61
AB  - OBJECTIVE: Characteristics of osteoarthritis (OA) include cartilage damage, 
      fibrosis, and osteophyte formation. Connective tissue growth factor (CTGF; also 
      known as CCN2), is found in high levels in OA chondrocytes and is frequently 
      involved in fibrosis, bone formation, and cartilage repair. The present study was 
      therefore undertaken to investigate the potential role of CTGF in OA 
      pathophysiology. METHODS: We transfected the synovial lining of mouse knee joints 
      with a recombinant adenovirus expressing human CTGF and measured synovial 
      fibrosis and proteoglycan content in cartilage on days 1, 3, 7, 14, and 28. 
      Messenger RNA (mRNA) expression in synovium and cartilage was measured on days 3, 
      7, and 21. RESULTS: CTGF induced synovial fibrosis, as indicated by accumulation 
      of extracellular matrix and an increase in procollagen type I-positive cells. The 
      fibrosis reached a maximum on day 7 and had reversed by day 28. Levels of mRNA 
      for matrix metalloproteinase 3 (MMP-3), MMP-13, ADAMTS-4, ADAMTS-5, tissue 
      inhibitor of metalloproteinases 1 (TIMP-1), and transforming growth factor beta 
      were elevated in the fibrotic tissue. TIMP-1 expression was elevated on day 3, 
      while expression of other genes did not increase until day 7 or later. CTGF 
      induced proteoglycan depletion in cartilage as early as day 1. Maximal depletion 
      was observed on days 3-7. Cartilage damage was reduced by day 28. A high level of 
      MMP-3 mRNA expression was found in cartilage. CTGF overexpression did not induce 
      osteophyte formation. CONCLUSION: CTGF induces transient fibrosis that is 
      reversible within 28 days. Overexpression of CTGF in knee joints results in 
      reversible cartilage damage, induced either by the high CTGF levels or via 
      factors produced by the CTGF-induced fibrotic tissue.
FAU - Blaney Davidson, E N
AU  - Blaney Davidson EN
AD  - St. Radboud University Medical Centre Nijmegen, Nijmegen, The Netherlands.
FAU - Vitters, E L
AU  - Vitters EL
FAU - Mooren, F M
AU  - Mooren FM
FAU - Oliver, N
AU  - Oliver N
FAU - Berg, W B van den
AU  - Berg WB
FAU - van der Kraan, P M
AU  - van der Kraan PM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Arthritis Rheum
JT  - Arthritis and rheumatism
JID - 0370605
RN  - 0 (CCN2 protein, human)
RN  - 0 (CCN2 protein, mouse)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 139568-91-5 (Connective Tissue Growth Factor)
SB  - IM
MH  - Animals
MH  - Cartilage/*pathology
MH  - Connective Tissue Growth Factor
MH  - Fibrosis
MH  - Immediate-Early Proteins/*biosynthesis
MH  - Intercellular Signaling Peptides and Proteins/*biosynthesis
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Synovial Membrane/*metabolism
EDAT- 2006/04/29 09:00
MHDA- 2006/08/05 09:00
CRDT- 2006/04/29 09:00
PHST- 2006/04/29 09:00 [pubmed]
PHST- 2006/08/05 09:00 [medline]
PHST- 2006/04/29 09:00 [entrez]
AID - 10.1002/art.21795 [doi]
PST - ppublish
SO  - Arthritis Rheum. 2006 May;54(5):1653-61. doi: 10.1002/art.21795.