Abstract
Bone morphogenetic proteins (BMPs) are multi-functional growth factors belonging to the transforming growth factor ss superfamily. Family members are expressed during limb development, endochondral ossification, early fracture, and cartilage repair. The activity of BMPs was first identified in the 1960s but the proteins responsible for bone induction were unknown until the purification and cloning of human BMPs in the 1980s. To date, about 15 BMP family members have been identified and characterized. The signal triggered by BMPs is transduced through serine/threonine kinase receptors, type I and II subtypes. Three type I receptors have been shown to bind BMP ligands, namely: type IA and IB BMP receptors and type IA activin receptors. BMPs seem to be involved in the regulation of cell proliferation, survival, differentiation and apoptosis, but their hallmark is their ability to induce bone, cartilage, ligament, and tendon formation at both heterotopic and orthotopic sites. This suggests that, in the future, they may play a major role in the treatment of bone diseases. Several animal studies have illustrated the potential of BMPs to enhance spinal fusion, repair critical-size defects, accelerate union, and heal articular cartilage lesions. Difficulties in producing and purifying BMPs from bone tissue have prompted the attempts made by several laboratories, including ours, to express these proteins in the recombinant form in heterologous systems. This review focuses on BMP structure, molecular mechanisms of action and significance and potential applications in medical, dental and veterinary practice for the treatment of cartilage and bone-related diseases.
Highlights
Since the discovery of bone morphogenetic proteins (BMPs) as bone inductive proteins by Urist [1], many investigators have shown that BMPs induce stem and mesenchymal cell differentiation into osteogenic cells capable of producing bone
The identity of osteogenic protein 1 (OP-1) and transforming growth factor ß (TGF-ß) is less than 38%, but it is 60 and 85%, respectively, relative to BMP-2 and BMP-5
Preliminary studies have reported that anti-recombinant human BMP (rhBMP)-2 was not produced after implantation of this recombinant protein in defects of the mandibles of dogs
Summary
Since the discovery of bone morphogenetic proteins (BMPs) as bone inductive proteins by Urist [1], many investigators have shown that BMPs induce stem and mesenchymal cell differentiation into osteogenic cells capable of producing bone. BMPs diffuse through a concentration gradient, thereby altering the developmental process. In response to this stimulus, the cells proliferate and differentiate following a pre-defined pattern and spatial arrangement. From a physical and chemical point of view, BMPs are proteins secreted by cells, which act as ligands for receptors present on the plasma membrane of different types of cells (autocrine and paracrine effects), establishing cell and tissue organization. The general role of BMPs in the process of bone formation during the development and repair of fractures has been well established. BMPs are capable of inducing the formation of bone tissue in ectopic sites and in critical-sized bone defects in several animal models. The objective of the present review was to clarify some of the basic aspects of the cellular and molecular mechanisms of action of BMPs, presenting some potential clinical applications and perspectives for their utilization
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