Cementogenesis and the induction of periodontal tissue regeneration by the osteogenic proteins of the transforming growth factor‐β superfamily

Abstract

The antiquity and severity of periodontal diseases are demonstrated by the hard evidence of alveolar bone loss in gnathic remains of the Pliocene/Pleistocene deposits of the Bloubank Valley at Sterkfontein, Swartkrans and Kromdrai in South Africa. Extant Homo has characterized and cloned a superfamily of proteins which include the bone morphogenetic proteins that regulate tooth morphogenesis at different stages of development as temporally and spatially connected events. The induction of cementogenesis, periodontal ligament and alveolar bone regeneration are regulated by the co-ordinated expression of bone morphogenetic proteins. Naturally derived and recombinant human bone morphogenetic proteins induce periodontal tissue regeneration in mammals. Morphological analyses on undecalcified sections cut at 3-6 mum on a series of mandibular molar Class II and III furcation defects induced in the non-human primate Papio ursinus show the induction of cementogenesis. Sharpey's fibers nucleate as a series of composite collagen bundles within the cementoid matrix in close relation to embedded cementocytes. Osteogenic protein-1 and bone morphogenetic protein-2 possess a structure-activity profile, as shown by the morphology of tissue regeneration, preferentially cementogenic and osteogenic, respectively. In Papio ursinus, transforming growth factor-beta(3) also induces cementogenesis, with Sharpey's fibers inserting into newly formed alveolar bone. Capillary sprouting and invasion determine the sequential insertion and alignment of individual collagenic bundles. The addition of responding stem cells prepared by finely mincing fragments of autogenous rectus abdominis muscle significantly enhances the induction of periodontal tissue regeneration when combined with transforming growth factor-beta(3) implanted in Class II and III furcation defects of Papio ursinus.

Developmental pathways of periodontal tissue regeneration

“…The high power view of connective tissue fibres representing the mesial and distal fibrous attachment shows insertion of perpendicularly oriented fibres tightly inserting into the dentinoid‐like material somehow resembling the oriented mammalian Sharpey's fibres with mesenchymal cells riding the fibres (Figure C,E).…”

“…Teeth and their fibrous attachment migrate mesially along with the conveyor belt moving away from the cartilaginous jaw (light blue arrow in A) until the tooth revolves around the tip of the cartilaginous jaw displaying severe dentinoclastic activity (blue/magenta arrow B) followed soon by tooth shedding. C,D, Details of C. obscurus ’ fibrous attachment; light blue arrows within the periodontal ligament system depict mesenchymal cells riding the fibres as indicated in periodontal ligament regeneration’ experiments in non‐human primates . D, Note the tight attachment of the fibres within the dentinoid‐mineralized material of the root of the tooth embedded in the fibrous attachment with elongated fibroblast‐like cells along the embedded fibres (light blue arrow in D).…”

“…D,E, Images courtesy of Xianghong Luan (Department of Oral Biology, University of Illinois, Chicago, Chicago, IL, USA). F‐K, Regenerating scenarios by the structure activity profile of different osteogenic soluble molecular signals of the TGF‐β supergene family . Amino acid sequence variations in the carboxy‐terminal assigns specialized pleiotropic activities to each protein based on the structure‐activity profile of each morphogenetic protein .…”

“…The crux of periodontal tissue regeneration, at least in extant mammals, is the induction of cementogenesis with the concurrent generation of bona fide Sharpey's fibres inserted into newly formed cementum. The assembly of a vascularized periodontal ligament system follows with oriented periodontal ligament fibres coursing from the bone matrix to the newly deposited cemental matrix or cementoid …”

Transforming Growth Factor-ß1 (TGF-ß1) immunoreactivity in heterotopic grafts of adult dental apical papilla.

“…Among the molecules that regulate the final stages of odontogenesis, the transforming growth factors superfamily (TGF) stands out, specially the transforming growth factor-beta 1 (TGF-ß1). It is involved in several stages of embryogenesis such as dental amelogenesis, controlling the expression of matrix metalloproteinases [7][8] , in cementogenesis and the regeneration of adult periodontal tissue 9 , in the differentiation of the odontoblasts and secretion of the predentina 10 . Differentiated odontoblasts secrete TGF-ß1 and regulate its activity in an autocrine manner 11 .…”