Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees

Zhang, Mi; Ghivizzani, Steven C.; Lechman, Eric L.; Glorioso, Joseph C.; Evans, Christopher H.; Robbins, Paul D.

doi:10.1186/ar745

Cited by 106 publications

(25 citation statements)

References 27 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In an attempt to increase the anabolic activity of chondrocytes in OA cartilage, different studies reported the use of growth factors and bone morphogenetic proteins (12). Although these agents have shown some beneficial effects, they generally have shortcomings that limit their clinical application (14,31,32).…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: A strategy to promote cartilage repair

Venkatesan

Barré

Bénani

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Osteoarthritis is a degenerative joint disease characterized by a progressive loss of articular cartilage components, mainly proteoglycans (PGs), leading to destruction of the tissue. We investigate a therapeutic strategy based on stimulation of PG synthesis by gene transfer of the glycosaminoglycan (GAG)-synthesizing enzyme, ␤1,3-glucuronosyltransferase-I (GlcAT-I) to promote cartilage repair. We previously reported that IL-1␤ down-regulated the expression and activity of GlcAT-I in primary rat chondrocytes. Here, by using antisense oligonucleotides, we demonstrate that GlcAT-I inhibition impaired PG synthesis and deposition in articular cartilage explants, emphasizing the crucial role of this enzyme in PG anabolism. Thus, primary chondrocytes and cartilage explants were engineered by lipid-mediated gene delivery to efficiently overexpress a human GlcAT-I cDNA. Interestingly, GlcAT-I overexpression significantly enhanced GAG synthesis and deposition as evidenced by 35 S-sulfate incorporation, histology, estimation of GAG content, and fluorophore-assisted carbohydrate electrophoresis analysis. Metabolic labeling and Western blot analyses further suggested that GlcAT-I expression led to an increase in the abundance rather than in the length of GAG chains. Importantly, GlcAT-I delivery was able to overcome IL-1␤-induced PG depletion and maintain the anabolic activity of chondrocytes. Moreover, GlcAT-I also restored PG synthesis to a normal level in cartilage explants previously depleted from endogenous PGs by IL-1␤-treatment. In concert, our investigations strongly indicated that GlcAT-I was able to control and reverse articular cartilage defects in terms of PG anabolism and GAG content associated with IL-1␤. This study provides a basis for a gene therapy approach to promote cartilage repair in degenerative joint diseases.osteoarthritis ͉ gene transfer ͉ chondrocyte ͉ glycosyltransferase ͉ glycosaminoglycan

show abstract

Section: Discussionmentioning

confidence: 99%

“…In this regard, local administration of transforming growth factor (TGF)-␤1 stimulated PG synthesis (13). However, adenovirus-mediated overexpression of TGF-␤1 in rabbit synovium failed to stimulate cartilage matrix synthesis and even produced cartilage degradation, suggesting that TGF-␤1 gene transfer may not be suitable for cartilage repair (14).…”

mentioning

confidence: 99%

Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: A strategy to promote cartilage repair

Venkatesan

Barré

Bénani

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Furthermore, it was reported that local injection of TGF-β in the synovial is associated with severe fibrosis, chondro-osteophyte formation (as mentioned above), the intrasynovial formation of cartilage and, paradoxically, loss of articular cartilage [157,158].…”

Section: Tgf-β Super-familymentioning

confidence: 94%

Cytokines and Growth Factors in the Treatment of Osteoarthritis: What Could be the Best Disease Modifying Drugs

Martel‐Pelletier

Tardif²,

Laufer³

et al. 2005

CMCAIAA

View full text Add to dashboard Cite

Osteoarthritis (OA) is by far the most prevalent arthritic disease affecting around 10% of the world's population and approximately 60% of 60-year-olds. It is also one of the most common arthritic diseases seen by general practitioners and rheumatologists. The increased frequency of OA with age, makes it a growing social health concern, as it is a disease associated with disability and pain. In the US today, the immediate cost of the disease is estimated at approximately 60 billion dollars a year. Despite the clinical success of non-steroidal anti-inflammatory drugs (NSAIDs) and of anti-cyclooxygenase (COX)-2 in treating symptoms, there is no cure for the disease to date. However, our knowledge of its etiopathogenesis has progressed significantly in the past few decades. Based on studies of human cells and animal models, targets for therapeutic intervention have been put forward and major efforts are underway to bring about new therapies that can reduce or stop the progression of the disease. This review should help the reader better understand the most recent advances regarding inflammatory and growth factors as new targets in reducing or stopping OA.

show abstract

“…An adverse effect was seen in a similar model overexpressing TGF-β. Intraarticular injection of an adenoviral vector carrying a TGFß construct caused extracellular matrix degradation and chondroblastic metaplasia in the synovial membrane [34,72].…”

Section: Transfection Of Synoviocytes and Mesenchymal Stem Cell Transfermentioning

confidence: 99%

Artificial Organs: A New Option for Treating Osteoarthritis

Stöve¹,

Lehmann²,

Fickert³

et al. 2007

CDD

View full text Add to dashboard Cite

Osteoarthritis is usually regarded as a localized disease whose optimal treatment is a therapy applied directly to the affected joint. Unfortunately, current local therapies such as repeated intraarticular injections or constant infusions are associated with a higher risk of infection. One way to overcome this would be to transfer substances made locally by cells within the joint. However, attempts using direct vector transfers or intraarticular injections of ex vivo modified cells could not achieve a sustained protein secretion over several months. Another method of delivering biological factors (i.e.growth hormones) intraarticularly is to transplant an artificial organ, capable of supporting the regeneration of natural cartilage, directly into the affected joint The main difficulty of having to produce bioactive factors over a long period of time is overcome by implanting a chamber-like system filled with either genetically modified cells or a drug-releasing matrix. This drug delivery system would be located at a peripheral site of the joint and could release substances directly into the joint cavity which would be transported via the synovial fluid and/or diffused to the chondrocytes or synoviocytes.

show abstract

Adverse effects of adenovirus-mediated gene transfer of human transforming growth factor beta 1 into rabbit knees

Cited by 106 publications

References 27 publications

Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: A strategy to promote cartilage repair

Stimulation of proteoglycan synthesis by glucuronosyltransferase-I gene delivery: A strategy to promote cartilage repair

Cytokines and Growth Factors in the Treatment of Osteoarthritis: What Could be the Best Disease Modifying Drugs

Artificial Organs: A New Option for Treating Osteoarthritis

Contact Info

Product

Resources

About