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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…

Overview of attention for article published in Molecular Medicine, December 2011
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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.

Twitter Demographics

The data shown below were collected from the profile of 1 tweeter who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Portugal 1 5%
Japan 1 5%
Unknown 19 90%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 7 33%
Unspecified 3 14%
Student > Master 2 10%
Student > Bachelor 2 10%
Professor > Associate Professor 2 10%
Other 5 24%
Readers by discipline Count As %
Agricultural and Biological Sciences 7 33%
Unspecified 4 19%
Biochemistry, Genetics and Molecular Biology 4 19%
Medicine and Dentistry 3 14%
Engineering 3 14%
Other 0 0%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. 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 15 September 2012.
All research outputs
#10,233,087
of 12,819,611 outputs
Outputs from Molecular Medicine
#453
of 586 outputs
Outputs of similar age
#89,007
of 125,936 outputs
Outputs of similar age from Molecular Medicine
#9
of 9 outputs
Altmetric has tracked 12,819,611 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
So far Altmetric has tracked 586 research outputs from this source. They typically receive a little more attention than average, with a mean Attention Score of 6.7. This one is in the 11th percentile – i.e., 11% of its peers scored the same or lower than it.
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