Bone Morphogenetic Proteins-An Update

Bone Morphogenetic Proteins(BMPs) are a group of growth factors and cytokines known for their ability to induce the formation of bone and cartilage.Originally seven such proteins were discovered.Of these six (BMP2 to BMP7)belong to TGF-B superfamily of proteins.BMP1 is a metalloprotease.Since then thirteen more BMPs have been discovered bringing the total to twenty.MarshallUrist proposed the name’BONEMORPHOGENETIC PROTEIN’ in thescientific literature in ‘Journal of Dental Research’in 1971.BMPs interact with specific receptors on the cell surface referred to as bone morphogenetic protein receptors(BMPRs).BMPs are now produced using recombinant DNA technology.BMP is the most promising osteoinductive protein for bone induction and regeneration. Recombinant human BMP(rhBMP) stimulates osteoblast differentiation in various cells in vitro and induces ectopic bone formation invivo.These formulations have found applications in many disciplines of medicine and dentistry.Orthopaedic and Oral surgery have benefitted greatly from commercially available BMP formulations in the last few years.


INTRODUCTION
Bone Morphogenetic Proteins (BMPs) are a group of growth factorsand cytokines which induces formation of bone and cartilage.Growth factor is a naturally occurring protein or steroid hormone capable of stimulating cellular growth, cellular differentiation and proliferation.They act as signaling molecules between cells that binds to specific receptors on the target cells.They promote cell differentiation and maturation which varies between growth factors.For example, Bone morphogenetic proteins stimulate bone cell differentiation while fibroblast growth factors and vascular endothelial growth factors stimulate blood vessel differentiation.Recombinant human BMPs (rhBMPs) are widely used in several tissueengineering products that might serve for the complete regeneration of bone or cartilage.

Discovery of BMP
Senn, a surgeon from Chicago , described

The BMP pathways
Bone Morphogenetic Proteins help in differentiation of cells and also in matrix production and vascularisation.

Functions and applications of BMPs
Bone Morphogenetic Proteins interact with specific receptors on the cell surfaces known as Since the evolution of reconstruction, maxillofacial surgeons could bring back the form and function of the bone resected due to pathologies associated with it.Various forms of reconstruction has since then been practised.From simple reconstruction plates to non vascularised bone grafts to vascularised free flaps,maxillofacial surgeons had options to choose which depended on their skills and the conditions warranted during those surgeries.Post surgical resection, boneresorption is inevitable which happens with varying degrees except in case of vascularised free flaps.When it comes to free flaps,the technique sensitivity and surgeon's skill play a key role.In such cases,preventingresorption and inducing bone formation was an able substitute to the technique sensitive free flaps.Bone morphogenetic proteins which are a group of growth factors help in osteo induction that is inducing bone producing osteoblasts to deposit bone at the native site.BMPs help in bone induction,differentiation and regeneration which can either form bone or cartilage.BMP2 to BMP7 belongs to Transforming growth factor beta superfamily of proteins.Thus BMPs prove to be a boon for reconstruction.

Courtesy
Improved Healing and Reduced Morbidity with Bone Morphogenic Protein-2 (BMP-2) In Older Patients with Alveolar Cleft Defects Brian P. Dickinson, MD, Kristy L. Wasson, BA, Catherine O'Hara, BS, JoubinGabbay, MD, Justin B. Heller, BS, and James P. Bradley, MD Serial roentgenograms of long term test animal demonstrating stability of rhBMP2 induced bone.Roentgenograms taken at 3(A) and 30(B)months after reconstruction.The bone remodelling that takes place over the 30 month period is evident.

CONCLUSION
Resection of diseased bone and replacement of lost structure to bring back form and function has been practised for many years since the evolution of reconstruction.Formation of new bone and cartilage was not possible with the preliminary form of reconstruction.Non vascularised bone grafts undergo resorption at the recipient site and replacement leading to decreased amount of bone deposition.Vascularised free flaps are technique sensitive and require good surgical acumen which also has its own complicarions such as flap necrosis.In order to bring back the native bone with the same form and function, osteoinduction,differentiation.maturationandregeneration of the recipient bone by Bone morphogenetic proteins play a vital role in reconstruction and are timetested till date.
BMP receptors.(BMPRs).The signal transduction through BMPRs result in mobilisation of members of SMAD family of Proteins.The signaling pathways involving BMPs,BMPRs and SMADs are important in the development of heart,CNS and cartilage, as well as post-natal bone development.They play an important role during embryonic development on the embryonic patterning and early skeletal formation.BMP4 and its inhibitors noggin and list of bone morphogenetic proteins BMP Known functions gene locus BMP1 Acts on procollagen I,II and III.Involved in C Chromosome : 8 artilage development.Location :8p21 BMP2 Acts as a disulfide -linked homodimer .Chromosome : 20 Induces bone and cartilage formation.Acts as a Location : 20p12 retinoid mediator.Key role in osteoblast differentiation.BMP3 Induces bone formation.Chromosome : 14 Location : 14p22 BMP4 Regulates formation of teeth,limbs and bone Chromosome :14 from mesoderm.Aids fracture repair.Location : 14q22-q23 BMP5 Acts in cartilage development.Chromosome : 6 Location : 6p12.1 BMP6 Plays a role in joint integrity in adults.Chromosome : 6 Location : 6p12.1 BMP7 Key role in osteoblast differentiation.Induces production of SMAD1.Chromosome : 20 Also in renal development and repair.Location : 20q13 BMP8a Involved in bone and cartilage development.polarity of the embryo (i.e.back and front patterning).Disruption of BMP signaling can affect body plan of developing embryo.Mutations in BMPs and their inhibitors (such as sclerostin) are associated with a number of human disorders which affect the skeleton.Bone Morphogenetic proteins have various applications in Oral and Maxillofacial Surgery.It has been used to reconstruct complete or partially resected mandible.It is used in facial clefts,cleft palate cases,alveolar ridge augmentation,cartilage repair in TMJ and in oral implants.Bone morphogenetic proteins produce osteo induction which helps in inducing osteoblasts to produce native bone or cartilage.