Pleiotropism of bone morphogenetic proteins: from bone induction to cementogenesis and periodontal ligament regeneration.

Bone morphogenetic and osteogenic proteins (BMPs/OPs), pleiotropic members of the transforming growth factor-beta (TGF-beta) supergene family, induce de novo endochondral bone formation and act as soluble signals of tissue morphogenesis, sculpting the architecture of multicellular mineralized structures, including the periodontal tissues. The presence of multiple forms of BMPs/OPs has a therapeutic significance and the choice of a suitable protein will be a formidable challenge to the practising periodontologist. Amino acid sequence variations in the carboxy terminal domain, the molecular basis of the structure/activity profile of each isoform, confer specialized and pleiotropic activities to each morphogenetic protein. Naturally derived BMPs/OPs regenerate cementum and alveolar bone in mandibular furcation defects of the primate Papio ursinus. Tissue morphogenesis induced by hOP-1 and hBMP-2 is qualitatively different when the morphogens are applied singly, indicating that the structure/activity profile amongst BMPs/OPs is controlling pleiotropic tissue induction and morphogenesis. Furcation defects of Papio ursinus with root surfaces exposed long-term to periodontal pathogens and filled with granulation tissue after inoculation of a pathogenetic human strain of Porphyromonas gingivalis twice a month for 12 months were implanted with hOP-1 osteogenic devices. Six months after surgery there was regeneration of alveolar bone and induction of cementogenesis, with Sharpey's fibres uniting the regenerated bone to the newly formed cementum. Although within the natural milieu of the bone matrix a plurality of morphogens may be required to initiate the cascade of pattern formation and the attainment of tissue form and function, recombinant y-irradiated hOP-1 delivered by a xenogeneic collagenous matrix induces complete periodontal tissue regeneration on periodontally affected root surfaces, showing an additional specific function of hOP-1 for tissue morphogenesis in clinical contexts. The pleiotropy of the signalling molecules of the TGF-beta superfamily is additionally highlighted by the redundancy of molecular signals initiating endochondral bone induction by the TGF-beta isoforms per se, powerful inducers of endochondral bone, but in the primate only. A novel approach in periodontal tissue regeneration is to induce heterotopic bone to be transplanted as morcellised autogenous grafts into established periodontal defects. The induction of bone develops a mosaic structure in which the osteogenic proteins of the TGF-beta superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis, with specific roles at different time points of the morphogenetic cascade.