The induction of bone formation: From bone morphogenetic proteins to the transforming growth factor-β3 protein - Redundancy, pleiotropy and the induction of cementogenesis

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DOI:

https://doi.org/10.17159/2519-0105/2021/v76no6a4

Keywords:

one morphogenetic proteins’ gene expression, qRTPCR, TGF-β3 master gene, noggin, molecular redundancy, pleiotropy, cementogenesis in angiogenesis, primates.

Abstract

This review proposes to translate organogenesis and the induction of bone formation by the recombinant human
transforming growth factor-β3 (hTGF-β3 ) in the Chacma baboon Papio ursinus to periodontal tissue induction and
regeneration. Naturally derived highly purified osteogenic proteins of the transforming growth factor-β (TGF-β) supergene family
were implanted in Class II furcation defects of the first and second mandibular molars. Additional defects in P.
ursinus were treated with recombinant human osteogenic protein-1 (hOP-1, also known as bone morphogenetic
protein-7, hBMP-7) and hBMP-2, singly or in binary applications. In different studies defects were also implanted with hTGF-β3
singly or in binary application with hOP-1. Harvested specimens on day 60 and 180 were processed for undecalcified histology using tungsten-carbide knives mounted on Polycut sledge’ micro-tomes or the Exakt precision cutting and grinding system.
Highly purified osteogenic proteins showed the induction of Sharpey’s fibres into newly formed cementoid with foci of mineralization. hOP-1 induced substantial cementogenesis whilst hBMP-2 preferentially induced alveolar bone. Intramuscular implantation of hTGF-β3 absorbed onto coral-derived macroporous bioreactors engineered large heterotopic multicellular bone organoids. Gene expression pathways by quantitative Reverse Transcription Polymerases Chain Reaction (qRT-PCR) show
that the induction of bone is via several profiled BMPs and TGF-βs expressed upon implantation of hTGF-β3 recapitulating the synergistic induction of bone as shown by binary applications of low doses of hTGF-β1 and hTGF-β3with hOP-1. The rapid induction of bone by hTGF-β3 provides theframework for a paradigmatic shift from recombinanthBMPs to hTGF-β3 in clinical contexts, provocatively operational in periodontal tissue regeneration with substantial induction of cementogenesis in angiogenesis.

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2021-07-31

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Ripamont, U. (2021). The induction of bone formation: From bone morphogenetic proteins to the transforming growth factor-β3 protein - Redundancy, pleiotropy and the induction of cementogenesis. South African Dental Journal, 76(06), 331-356. https://doi.org/10.17159/2519-0105/2021/v76no6a4