Osteogenic Proteins of the TGF-β Superfamily

Ripamonti, Ugo

doi:10.1016/b0-12-341103-3/00319-3

Cited by 30 publications

(199 citation statements)

References 9 publications

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“…In marked contrast to the rodent bioassay, the TGF-β isoforms so far tested in our laboratories have shown a marked site and tissuespecific endochondral osteoinductivity in the pri-mate Papio ursinus. Remarkably this occurs in primates only [2,10,12,[20][21][22][23] (Fig. 1C).…”

Section: Species Site and Tissue Specificitymentioning

confidence: 99%

“…The presence of several molecular forms with osteogenic activity poses important questions about the biological significance of this apparent redundancy [10], indicating multiple interactions, or cross-talk between components of the signalling pathways initiating de novo bone formation and tissue morphogenesis in primate species.…”

Section: Bone Induction By Tgf-β β Family Membersmentioning

confidence: 99%

“…Thus osteogenesis can occur via the combined action of several BMPs/OPs resident within the natural milieu of the extracellular matrix of bone [7,[10][11][12] (Fig. 1B).…”

Section: Bone Induction By Tgf-β β Family Membersmentioning

confidence: 99%

“…1C). In this animal model, the induction of bone by TGF-β isoforms is characterised by a marked site and tissue specificity [2,10,12,[20][21][22][23].…”

Section: Bone Induction By Tgf-β β Family Membersmentioning

confidence: 99%

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Soluble, insoluble and geometric signals sculpt the architecture of mineralized tissues

Ripamonti

2004

J Cellular Molecular Medi

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Bone morphogenetic and osteogenic proteins (BMPs/OPs), members of the transforming growth factor-β (TGF-β) superfamily, are soluble mediators of tissue morphogenesis and induce de novo endochondral bone formation in heterotopic extraskeletal sites as a recapitulation of embryonic development. In the primate Papio ursinus, the induction of bone formation has been extended to the TGF-β isoforms per se. In the primate and in the primate only, the TGF-β isoforms are initiators of endochondral bone formation by induction and act in a species-, site-and tissuespecific mode with robust endochondral bone induction in heterotopic sites but with limited new bone formation in orthotopic bone defects. The limited inductive capacity orthotopically of TGF-β isoforms is associated with expression of the inhibitory Smads, Smad6 and Smad7. In primates, bone formation can also be induced using biomimetic crystalline hydroxyapatite matrices with a specific surface geometry and without the exogenous application of osteogenic proteins of the TGF-β superfamily, even when the biomimetic matrices are implanted heterotopically in the rectus abdominis muscle. The sequence of events that directs new bone formation upon the implantation of highly crystalline biomimetic matrices initiates with vascular invasion, mesenchymal cell migration, attachment and differentiation of osteoblast-like cells attached to the substratum, expression and synthesis of osteogenic proteins of the TGF-β superfamily resulting in the induction of bone as a secondary response. The above findings in the primate indicate enormous potential for the bioengineering industry. Of particular interest is that biomimetic matrices with intrinsic osteoinductivity would be an affordable option in the local context.

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Section: Species Site and Tissue Specificitymentioning

confidence: 99%

Section: Bone Induction By Tgf-β β Family Membersmentioning

confidence: 99%

“…Thus osteogenesis can occur via the combined action of several BMPs/OPs resident within the natural milieu of the extracellular matrix of bone [7,[10][11][12] (Fig. 1B).…”

Section: Bone Induction By Tgf-β β Family Membersmentioning

confidence: 99%

“…1C). In this animal model, the induction of bone by TGF-β isoforms is characterised by a marked site and tissue specificity [2,10,12,[20][21][22][23].…”

Section: Bone Induction By Tgf-β β Family Membersmentioning

confidence: 99%

See 2 more Smart Citations

Soluble, insoluble and geometric signals sculpt the architecture of mineralized tissues

Ripamonti

2004

J Cellular Molecular Medi

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158

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“…The BMPs/OPs are a family of highly conserved secreted pleiotropic proteins that initiate cartilage and bone formation in vivo [1][2][3][4][5][6][7] BMPs/OPs are members of the transforming growth factor-β (TGF-β) superfamily and play critical roles as soluble mediators of tissue morphogenesis [1][2][3][4][5][6][7][8][9]. In addition to post-natal osteogenesis, BMPs/OPs play multiple roles in embryonic development and are involved in inductive events unrelated to bone induction that control pattern formation during embryonic organogenesis [2][3][4][5][6][7][8][9].…”

mentioning

confidence: 99%

Bone induction by recombinant human osteogenic protein-1 (hOP-1, BMP-7) in the primate Papio ursinus with expression of mRNA of gene products of the TGF-? superfamily

Ripamonti

2005

J Cellular Mol Med

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Predictable bone induction in clinical contexts requires information on the expression and cross regulation of gene products of the transforming growth factor‐β (TGF‐β) superfamily elicited by single applications of each recombinant human bone morphogenetic/ostegenic proteins (BMPs/OPs). Using the calvarium and the rectus abdominis muscle of adult baboons Papio ursinus as a model for tissue induction and morphogenesis, this study investigated the induction of bone morphogenesis by γ‐irradiated hOP‐1 delivered by γ‐irradiated bovine insoluble collagenous bone matrix, the hOP‐1 osteogenic device, for bone induction in heterotopic and orthotopic sites of the primate Papio ursinus and the expression patterns of OP‐1, collagen type IV, BMP‐3 and TGFβ1mRNAs elicited by increasing single applications of doses of the hOP‐1 osteogenic devices (0.1, 0.5 and 2.5 mg hOP‐1/g of matrix) applied heterotopically in the rectus abdominis muscle and orthotopically in 48 calvarial defects of 12 adult baboons. Histology and histomorphometry on serial undecalcified sections prepared from the specimens harvested on day 15, 30 and 90 showed that all the doses of the hOP‐1 osteogenic device induced bone formation culminating in complete calvarial regeneration by day 90. Type IV collagen mRNA expression, a marker of angiogenesis, was strongly expressed in both heterotopic and orthotopic tissues. High levels of expression of OP‐1 mRNA demonstrated autoinduction of OP‐1 mRNAs. Expression levels of BMP‐3 mRNA varied from tissues induced in heterotopic vs. orthotopic sites with high expression in rapidly forming heterotopic ossicles together with high expression of type IV collagen mRNA. The temporal and spatial expressions of TGF‐β1 mRNA indicate a specific temporal transcriptional window during which expression of TGF‐β1 is mandatory for successful and optimal osteogenesis. The induction of bone by hOP‐1 in Papio ursinus develops as a mosaic structure with distinct spatial and temporal patterns of gene expression of members of the TGF‐β superfamily that singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis.

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