Role of bone morphogenetic proteins in periodontal tissue engineering: Relatively unexplored horizon

1 Introduction

Regeneration of the periodontal tissues following destructive episodes of various forms of periodontitis is a formidable challenge to periodontologists. the, gingival unit spontaneously regenerates with a junctional epithelial component of varying height following any kind of periodontal treatment, provided the root surface is adequately decontaminated, but the initiation and promotion of osteogenesis is a problem central to periodontal regeneration. Tissue engineering is the emerging field of science aimed at developing techniques for the fabrication of new tissues to replace damaged tissues and is based on principles of cell biology, developmental biology and biomaterials science [1, 2]. Periodontal tissue engineering foremost entails the induction of cementogenesis and the genesis of Sharpey’s fibers inserting into newly formed cementum [3].

Research into the molecular initiators of bone differentiation has culminated in the identification of an entirely new family of proteins, the bone morphogenetic proteins that regulate cartilage and bone differentiation. The bone morphogenetic proteins are the only morphogens “thus far found in mammalian species and are detected not only in the embryonic, but also post fetal bone development” [4, 5].

2 Structure of bone morphogenetic proteins

Bone morphogenetic proteins are members of TGF-β (Transforming growth factor-β) super family, a large family of growth factors. The TGF-β was so named because of its ability to transform cultured fibroblasts [6]. At their carboxy-terminal ends, all BMPs possess a region containing seven cysteine residues in the TGF-β superfamily. Synthesis of BMP takes place inside the cell in precursor form, which has hydrophobic stretch of 50-100 amino acids. Before secretion out of the cell, it consists of single peptide, pro-peptide, pro-domain and mature peptide once the cleavage of the signal peptide occurs, the precursor protein undergoes glycosylation and dimerization. On secretion of the mature bioactive dimeric BMP by the cell, the pro-domain is cleaved. The mature BMP derives from the carboxy terminal region by proteolytical cleavage and are secreted as either heterodimers or homodimers [7].

3 Classification of bone morphogenetic proteins

The human genome encodes 20 BMPs [6]. The first subclass contains BMP–2 and BMP–4, highly related molecules that differ mainly in the amino terminal region, with BMP-2 containing a heparin-binding domain. The second subclass consists of BMP-5, BMP-6, and BMP-7, also known as osteogenic protein-1 (OP-1), and BMP-8 (OP-2). These are slightly larger proteins than BMP-2 and BMP-4, and there is an approximate 78% amino acid identity between the subgroups. In the third subclass, and more distantly related to these factors, is BMP-3, also called osteogenin. Proof that these proteins were responsible for the bone inductive activity in bone matrix was found in the recombinant expression of each of these proteins [8].

4 Perspectives in periodontal tissue engineering by BMPs

Several studies have highlighted that partially purified and purified extracts of cementum contain a mitogenic growth factor as a distinct molecular species. The presence of mitogenic growth factors within the cemental matrix indicates that cementum has the potential to regulate the adjacent periodontal ligament space [9]. The extracellular matrix of the cementum may provide a framework for the regeneration of the various tissue components of the periodontal ligament and, in addition, may play important physiological roles in sequestration of morphogenetic factors involved in repair, regeneration and remodeling [10].

It will be of importance to bioassay cemental extracts after 6 M guanidinium or urea dissociative extraction followed by heparin–Sepharose affinity chromatography. Cemental extracts purified by affinity chromatography may retain osteogenic proteins embedded within the matrix as a memory of developmental events, as highlighted by demineralized dentine matrix of P. ursinus with osteogenic activity in the rectus abdominis. If cementum does induce endochondral bone differentiation, it would be tempting to suggest that bone induction modulated by cemental matrices may be the result of a slow release of embryonic remnants of osteogenic proteins that were required and deployed during cementogenesis [5].

This mammalian BMP initiates programmed cellular events which results in induction of bone which is functionally conserved process utilized in embryonic development, recapitulated in post-fetal osteogenesis and can be re-exploited for the therapeutic initiation of periodontal tissue regeneration. There are several challenges that provide opportunities to gain mechanistic insights into the regulation of periodontal tissue regeneration; a challenge of great molecular importance is the biological significance of apparent redundancy. The presence of the structure activity profile amongst soluble osteogenic molecular signals indicates a therapeutic significance in contexts to clinical outcome. Significant advances in periodontal tissue regeneration may be expected if ongoing and future research is tailored to provide further mechanistic insights into the relevance of apparent redundancy and the structure–activity profile of the recombinant human osteogenic proteins. Nonetheless, at the beginning of the 21st century, a soluble osteogenic and recombinant molecular signal, when combined with an insoluble signal, triggers periodontal tissue regeneration with the induction of cementogenesis and insertion of Sharpey’s fibers, essential ingredients to engineer periodontal tissue regeneration [11, 12].

5 Conclusion

The presence of the structural activity of bone morphogenetic proteins amongst soluble osteogenic molecular signals indicates a therapeutic significance in clinical contexts. The challenge lies in applying these drugs with consistent success in various applications. Further, studies are needed for development of carrier materials that have mechanical properties and surgical practicality appropriate for controlled release of bone morphogenetic proteins which will enhance use of tissue engineering in periodontal tissue regeneration.