Bone morphogenetic proteins, cementogenesis, myoblastic stem cells and the induction of periodontal tissue regeneration

Abstract

‘ Bone: Formation by autoinduction’, initiates by invocation of soluble molecular signals which, when combined to insoluble signals or substrata trigger the ripple-like cascade of bone differentiation by induction. The osteogenic proteins of the transforming growth factor-β (TGF-β) superfamily, the bone morphogenetic/osteogenic proteins (BMPs/OPs), and uniquely in the non-human primate Papio ursinus also the three mammalian TGF-β isoforms, induce endochondral bone formation as recapitulation of embryonic development. The pleiotropic activities of the BMPs/OPs are vast and include the induction of periodontal tissue regeneration. Implantation of naturally derived highly purified osteogenic fractions after sequential adsorption/affinity and gel filtration chromatography in mandibular Class II furcation defects of P. ursinus induces cementogenesis as highly cellular collagenic cementoid attached to the exposed dentine with foci of nascent mineralization with inserted de novo generated Sharpey's fibres. Recombinant human osteogenic protein-1 (hOP-1) when implanted in Class II furcation defects of P. ursinus with surgically exposed dentine matrix preferentially initiates the induction of cementogenesis; on the other hand, hBMP-2 preferentially induces alveolar bone regeneration with mineralized bone covered by prominent osteoid seams. Long-term studies with gamma-irradiated 0.5 and 2.5 mg hOP-1 per gram of xenogeneic bovine collagenous matrix induce the restitutio ad integrum of the periodontal tissues in furcation defects exposed by chronic periodontitis in P. ursinus. A challenging question for tissue engineering and regenerative medicine is whether the presence of molecularly different osteogenic proteins of the TGF-β superfamily has a therapeutic significance. Mechanistically, the specificity of hOP-1 primarily initiating cementogenesis in periodontal defects is regulated by both the dentine extracellular matrix upon which responding cells attach and differentiate, and the structure/activity profile of the implanted hOP-1; the limited induction of cementogenesis by hBMP-2 in furcation defects of non-human primate and canine models is consistent with the reported data that hBMP-2 inhibits differentiation and mineralization of cementoblasts in vitro aside the specific structure/activity profile of the implanted hBMP-2 protein. The induction of periodontal tissue regeneration develops as a mosaic structure in which the osteogenic proteins of the TGF-β superfamily singly, synergistically and synchronously initiate and maintain tissue induction and morphogenesis as a recapitulation of embryonic development.