| Title |
Benefits of Recombinant Adeno-Associated Virus (rAAV)-Mediated Insulinlike Growth Factor I (IGF-I) Overexpression for the Long-Term Reconstruction of Human Osteoarthritic Cartilage by Modulation of the IGF-I Axis
|
|---|---|
| Published in |
Molecular Medicine, December 2011
|
| DOI | 10.2119/molmed.2011.00371 |
| Pubmed ID | |
| Authors |
Anja Weimer, Henning Madry, Jagadeesh K. Venkatesan, Gertrud Schmitt, Janina Frisch, Anna Wezel, Jochen Jung, Dieter Kohn, Ernest F Terwilliger, Stephen B. Trippel, Magali Cucchiarini |
| Abstract |
Administration of therapeutic genes to human osteoarthritic (OA) cartilage is a potential approach to generate effective, durable treatments against this slow, progressive disorder. Here, we tested the ability of recombinant adeno-associated virus (rAAV)-mediated overexpression of human insulinlike growth factor (hIGF)-I to reproduce an original surface in human OA cartilage in light of the pleiotropic activities of the factor. We examined the proliferative, survival and anabolic effects of the rAAV-hIGF-I treatment in primary human normal and OA chondrocytes in vitro and in explant cultures in situ compared with control (reporter) vector delivery. Efficient, prolonged IGF-I secretion via rAAV stimulated the biological activities of OA chondrocytes in all the systems evaluated over extended periods of time, especially in situ, where it allowed for the long-term reconstruction of OA cartilage (at least for 90 d). Remarkably, production of high, stable amounts of IGF-I in OA cartilage using rAAV advantageously modulated the expression of central effectors of the IGF-I axis by downregulating IGF-I inhibitors (IGF binding protein [IGFBP]-3 and IGFBP4) while up-regulating key potentiators (IGFBP5, the IGF-I receptor and downstream mitogen-activated protein kinase/extracellular signal-regulated kinase 1/2 [MAPK/ERK-1/2] and phosphatidylinisitol-3/Akt [PI3K/Akt] signal transduction pathways), probably explaining the enhanced responsiveness of OA cartilage to IGF-I treatment. These findings show the benefits of directly providing an IGF-I sequence to articular cartilage via rAAV for the future treatment of human osteoarthritis. |
X Demographics
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Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United States | 1 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 1 | 100% |
Mendeley readers
The data shown below were compiled from readership statistics for 33 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Japan | 1 | 3% |
| Portugal | 1 | 3% |
| Unknown | 31 | 94% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 7 | 21% |
| Researcher | 5 | 15% |
| Student > Doctoral Student | 3 | 9% |
| Student > Master | 3 | 9% |
| Student > Bachelor | 2 | 6% |
| Other | 3 | 9% |
| Unknown | 10 | 30% |
| Readers by discipline | Count | As % |
|---|---|---|
| Agricultural and Biological Sciences | 7 | 21% |
| Medicine and Dentistry | 5 | 15% |
| Biochemistry, Genetics and Molecular Biology | 4 | 12% |
| Engineering | 2 | 6% |
| Business, Management and Accounting | 1 | 3% |
| Other | 2 | 6% |
| Unknown | 12 | 36% |
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 03 May 2022.
All research outputs
#6,914,676
of 22,678,224 outputs
Outputs from Molecular Medicine
#326
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Outputs of similar age
#63,188
of 240,840 outputs
Outputs of similar age from Molecular Medicine
#10
of 19 outputs
Altmetric has tracked 22,678,224 research outputs across all sources so far. This one has received more attention than most of these and is in the 68th percentile.
So far Altmetric has tracked 1,126 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.1. This one has gotten more attention than average, scoring higher than 69% of its peers.
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