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

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 morphogeneticprotein-7, hBMP-7) and hBMP-2, singly or in binary applications. In different studies defects were also implanted with hTGF-β3singly 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.