Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2016-09-01
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| Series: | Frontiers in Physiology |
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| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00396/full |
| _version_ | 1819156361420734464 |
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| author | Ugo Ripamonti Raquel Duarte Ruqayya Parak Caroline Dickens Therese Dix-Peek Roland Manfred Klar Roland Manfred Klar |
| author_facet | Ugo Ripamonti Raquel Duarte Ruqayya Parak Caroline Dickens Therese Dix-Peek Roland Manfred Klar Roland Manfred Klar |
| author_sort | Ugo Ripamonti |
| collection | DOAJ |
| description | 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 Papio 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. |
| first_indexed | 2024-12-22T15:51:39Z |
| format | Article |
| id | doaj.art-03f0dc80b13142acb0aafdbd3570a064 |
| institution | Directory Open Access Journal |
| issn | 1664-042X |
| language | English |
| last_indexed | 2024-12-22T15:51:39Z |
| publishDate | 2016-09-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Physiology |
| spelling | doaj.art-03f0dc80b13142acb0aafdbd3570a0642022-12-21T18:20:53ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2016-09-01710.3389/fphys.2016.00396175232Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoformUgo Ripamonti0Raquel Duarte1Ruqayya Parak2Caroline Dickens3Therese Dix-Peek4Roland Manfred Klar5Roland Manfred Klar6University of the Witwatersrand, JohannesburgUniversity of the WitwatersrandUniversity of the WitwatersrandUniversity of the WitwatersrandUniversity of the WitwatersrandUniversity of the Witwatersrand, JohannesburgUniversity of the WitwatersrandThe 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 Papio 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.http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00396/fullPrimatesTransforming Growth Factor beta3molecular evolutionredundancyInduction of bone formation |
| spellingShingle | Ugo Ripamonti Raquel Duarte Ruqayya Parak Caroline Dickens Therese Dix-Peek Roland Manfred Klar Roland Manfred Klar Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform Frontiers in Physiology Primates Transforming Growth Factor beta3 molecular evolution redundancy Induction of bone formation |
| title | Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform |
| title_full | Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform |
| title_fullStr | Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform |
| title_full_unstemmed | Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform |
| title_short | Redundancy and molecular evolution: the rapid Induction of bone formation by the mammalian transforming growth factor-β3 isoform |
| title_sort | redundancy and molecular evolution the rapid induction of bone formation by the mammalian transforming growth factor β3 isoform |
| topic | Primates Transforming Growth Factor beta3 molecular evolution redundancy Induction of bone formation |
| url | http://journal.frontiersin.org/Journal/10.3389/fphys.2016.00396/full |
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