PMID- 16284937
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20060123
LR  - 20191109
IS  - 1473-2262 (Electronic)
IS  - 1473-2262 (Linking)
VI  - 10
DP  - 2005 Nov 14
TI  - Adeno-associated vector mediated gene transfer of transforming growth 
      factor-beta1 to normal and osteoarthritic human chondrocytes stimulates cartilage 
      anabolism.
PG  - 40-50
AB  - The objective of the present study was to investigate whether cartilage anabolism 
      in human primary osteoarthritic chondrocytes could be improved by 
      adeno-associated virus (AAV) vector-mediated gene transduction of transforming 
      growth factor TGF-beta1 (TGF-beta1). A bi-cistronic AAV-TGF-beta1-IRES-eGFP 
      (AAV-TGF-beta1) vector was generated and used for transduction of a normal human 
      articular chondrocyte cell line (tsT/AC62) and primary human osteoarthritic 
      articular chondrocytes harvested from 8 patients receiving total knee joint 
      arthroplasty. Transduction efficiency was detected by fluorescent microscopy for 
      gene expression of enhanced green fluorescent protein (eGFP). TGF-beta1 synthesis 
      was determined by ELISA. To assess the influence of TGF-beta1 gene therapy on 
      chondrocyte cartilage metabolism, mRNA expressions of type II collagen, aggrecan, 
      and matrix metalloproteinase 3 (MMP-3) were determined by quantitative real-time 
      PCR. AAV-TGF-beta1 transduction resulted in increased synthesis of TGF-beta1 in 
      both osteoarthritic chondrocytes and the normal articular chondrocyte cell line. 
      The expression levels of the transduced genes were correlated to "multiplicity of 
      infection" (MOI) and post-infectious time. In both osteoarthritic chondrocytes 
      and the normal articular chondrocyte cell line, AAV-TGF-beta1 treatment increased 
      mRNA expression of both type II collagen and aggrecan, but decreased MMP-3 mRNA 
      expression. Osteoarthritic chondrocytes and the normal articular chondrocyte cell 
      line could be transduced with equal efficiencies. In conclusion, it was 
      demonstrated that AAV-TGF-beta1 gene transfer stimulates cartilage anabolism and 
      decreases expression of enzymes responsible for cartilage degradation in human 
      osteoarthritic chondrocytes. The results indicate that the AAV vector is an 
      efficient mediator of growth factors to human articular chondrocytes, and that it 
      might be useful in future chondrocyte gene therapy.
FAU - Ulrich-Vinther, M
AU  - Ulrich-Vinther M
AD  - Department of Orthopaedics, Aarhus University Hospital, Tage Hansens Gade 2, 
      DK-8000 Aarhus C, Denmark. ulrich-vinther@mail.dk
FAU - Stengaard, C
AU  - Stengaard C
FAU - Schwarz, E M
AU  - Schwarz EM
FAU - Goldring, M B
AU  - Goldring MB
FAU - Soballe, K
AU  - Soballe K
LA  - eng
PT  - Journal Article
DEP - 20051114
PL  - United States
TA  - Eur Cell Mater
JT  - European cells & materials
JID - 100973416
EDAT- 2005/11/15 09:00
MHDA- 2005/11/15 09:01
CRDT- 2005/11/15 09:00
PHST- 2005/11/15 09:00 [pubmed]
PHST- 2005/11/15 09:01 [medline]
PHST- 2005/11/15 09:00 [entrez]
AID - vol010a05 [pii]
AID - 10.22203/ecm.v010a05 [doi]
PST - epublish
SO  - Eur Cell Mater. 2005 Nov 14;10:40-50. doi: 10.22203/ecm.v010a05.