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Redundancy and Molecular Evolution: The Rapid Induction of Bone Formation by the Mammalian Transforming Growth Factor-β3 Isoform

Overview of attention for article published in Frontiers in Physiology, September 2016
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Title
Redundancy and Molecular Evolution: The Rapid Induction of Bone Formation by the Mammalian Transforming Growth Factor-β3 Isoform
Published in
Frontiers in Physiology, September 2016
DOI 10.3389/fphys.2016.00396
Pubmed ID
Authors

Ugo Ripamonti, Raquel Duarte, Ruqayya Parak, Caroline Dickens, Therese Dix-Peek, Roland M. Klar

Abstract

The soluble osteogenic molecular signals of the transforming growth factor-β (TGF-β) supergene family are the molecular bases of the induction of bone formation and postnatal bone tissue morphogenesis with translation into clinical contexts. The mammalian TGF-β3 isoform, a pleiotropic member of the family, controls a vast array of biological processes including the induction of bone formation. Recombinant hTGF-β3 induces substantial bone formation when implanted with either collagenous bone matrices or coral-derived macroporous bioreactors in the rectus abdominis muscle of the non-human primate Papio ursinus. In marked contrast, the three mammalian TGF-βs do not initiate the induction of bone formation in rodents and lagomorphs. The induction of bone by hTGF-β3/preloaded bioreactors is orchestrated by inducing fibrin-fibronectin rings that structurally organize tissue patterning and morphogenesis within the macroporous spaces. Induced advancing extracellular matrix rings provide the structural anchorage for hyper chromatic cells, interpreted as differentiating osteoblasts re-programmed by hTGF-β3 from invading myoblastic and/or pericytic differentiated cells. Runx2 and Osteocalcin expression are significantly up-regulated correlating to multiple invading cells differentiating into the osteoblastic phenotype. Bioreactors pre-loaded with recombinant human Noggin (hNoggin), a BMPs antagonist, show down-regulation of BMP-2 and other profiled osteogenic proteins' genes resulting in minimal bone formation. Coral-derived macroporous constructs preloaded with binary applications of hTGF-β3 and hNoggin also show down-regulation of BMP-2 with the induction of limited bone formation. The induction of bone formation by hTGF-β3 is via the BMPs pathway and it is thus blocked by hNoggin. Our systematic studies in P. ursinus with translational hTGF-β3 in large cranio-mandibulo-facial defects in humans are now requesting the re-evaluation of "Bone: formation by autoinduction" in primate models including humans.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 17 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 17 100%

Demographic breakdown

Readers by professional status Count As %
Professor 3 18%
Student > Ph. D. Student 3 18%
Student > Master 2 12%
Other 1 6%
Lecturer > Senior Lecturer 1 6%
Other 3 18%
Unknown 4 24%
Readers by discipline Count As %
Medicine and Dentistry 4 24%
Biochemistry, Genetics and Molecular Biology 3 18%
Agricultural and Biological Sciences 2 12%
Earth and Planetary Sciences 1 6%
Unknown 7 41%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 2. 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 24 September 2016.
All research outputs
#14,860,134
of 22,886,568 outputs
Outputs from Frontiers in Physiology
#5,706
of 13,679 outputs
Outputs of similar age
#201,930
of 332,538 outputs
Outputs of similar age from Frontiers in Physiology
#60
of 160 outputs
Altmetric has tracked 22,886,568 research outputs across all sources so far. This one is in the 33rd percentile – i.e., 33% of other outputs scored the same or lower than it.
So far Altmetric has tracked 13,679 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 7.6. This one has gotten more attention than average, scoring higher than 51% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 332,538 tracked outputs that were published within six weeks on either side of this one in any source. This one is in the 36th percentile – i.e., 36% of its contemporaries scored the same or lower than it.
We're also able to compare this research output to 160 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 60% of its contemporaries.