title: Biological aspects of periodontal tissue regeneration: cementogenesis and the induction of Sharpey's fibres.
abstract: The realm of periodontal tissue regeneration has a plethora of unanswered questions and challenges due to the complexity of restoring mineralised and fibrous connective tissues ultimately to be covered by epithelium in a very specific spatial organisation. Wound healing of the periodontium follows a highly ordered sequence of events that guides cellular morphology, differentiation, migration and proliferation and comprises a series of cellular, extracellular and molecular reciprocal interactions. The prerequisite for regeneration of any structure is the trio of a soluble molecular signal, a scaffold and responding stem cells. Striated muscle represents an abundant source of easily accessible tissue that contains several perivascular, pericytic and myoblastic cell niches capable of differentiating and inducing selected tissue phenotypes and morphogenesis. Morcellated autogenous rectus abdominis muscle combined with 75 microg of hTGF-beta3 in Matrigel matrix implanted into non-human primate class II and III furcation defects induced greater alveolar bone formation and cementogenesis when compared to furcation defects without the addition of morcellated autogenous bone. In situ hybr disation and immunohistochemistry during embryonic development and tooth morphogenesis have shown synchronous but spatially different bone morphogenetic proteins (BMPs) expression during tissue induction and morphogenesis. Preclin cal studies in the non-human primate Papio ursinus have shown a seemingly specific cementogenic function of osteogenic protein-1 (OP-1, also known as BMP-7) when treating Class II furcation defects of Papio ursinus. In context, hOP-1 is preferentially cementogenic when implanted into non-human primate class II and III furcation defects whilst hBMP-2 is highly osteogenic but not cementogenic when in contact with dentine extracellular matrix. Importantly, naturally-derived highly purified BMPs/OPs, recombinant hOP-1 and hTGF-beta3 when implanted into non-human primates Class II and III furcation defects induce cementogenesis with morphologically and functionally oriented periodontal ligament fibres coursing within a newly formed highly vascular periodontal ligament space with Sharpey's fibres generated within the newly secreted cementoid matrix. The grand challenge of molecular and therapeutic implications is the biological significance of apparent redundancy. The presence of several homologous but molecularly different isoforms all endowed with the striking capacity of inducing "bone formation by autoinduction" indicates that there is a structure/activity profile amongst soluble osteogenic molecular signals; this suggests a therapeutic significance in clinical contexts. The structure/activity profile finely tunes the vast pleiotropic activities of the soluble molecular signals in mineralised and non-mineralised tissues profoundly modulating epithelial/mesenchymal tissue interactions. Significant advances in regenerative tissue engineering may be expected if ongoing research is tailored to provide further mechanistic and morphological insights into the relevance of the apparent redundancy and the structure/activity profile of the recombinant human osteogenic proteins. The presence of the structure/activity profile together with the biological significance of apparent redundancy will necessitate re-shaping and re-engineering developing newly devised targeted therapeutics for periodontal tissue engineering.
authors.affiliation: Bone Research Laboratory, School of Physiology, Faculty of Heath Sciences; University of the Witwatersrand, Johannesburg.
authors.forename: A
authors.initials: A
authors.lastname: Magan
authors.forename: U
authors.initials: U
authors.lastname: Ripamonti
mesh_terms: D000539:Alveolar Process / Q000254:growth & development* / Q000648:ultrastructure; D025021:Cementogenesis / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D010012:Osteogenesis / Q000502:physiology*; D010513:Periodontal Ligament / Q000502:physiology; D010519:Periodontium / Q000502:physiology*; D012038:Regeneration / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D013234:Stem Cells / Q000502:physiology; D023822:Tissue Engineering / Q000379:methods
chemical_list: D036341:Intercellular Signaling Peptides and Proteins