Bone Morphogenetic Proteins: Basic Concepts
Bone Morphogenetic Proteins: Basic Concepts
The cellular and molecular events governing bone formation in the embryo, healing of a fractured bone, and induced bone fusion follow a similar pattern. Discovery, purification, and recombinant synthesis of bone morphogenetic proteins (BMPs) constiute a major milestone in the understanding of bone physiology. In this review the author discusses the mechanism of action, clinical applications, dosage, and optimum carriers for BMPs. The roles played by other growth factors are also discussed.
Bone is unique of all the tissues in the in the vertebrate organism. When injured, it heals by formation of new bone. In contrast, most other tissues such as the heart muscle, voluntary muscles, liver, and the brain heal by replacement of connective tissue rather than the original tissue.
Another interesting attribute of the bone is that the molecular and cellular processes that lead to the development of the skeletal structures within the embryo are very similar to the cascades that occur in the healing process in an injured bone. Likewise, in surgically created fusion, the osseous fusion mass formation recapitulates a fracture healing process, which in turn recapitulates embryonic development of new bone. Thus, there is a common theme in the development of bone from primitive mesenchymal tissues to a well-structured, well-organized histological structure that one associates with mature bone. In addition, the ongoing remodeling process in an adult organism, which is exposed to external physical and hormonal influences, is also modulated through a similar molecular mechanism.
The developing limb bud represents a prototypical example of bone development in the embryo. There is a condensation of primitive mesenchymal cells in the central core of the limb bud, in the area destined to form skeletal structures. This condensation usually transforms into bone through two independent pathways. Intramembranous ossification occurs when there is a direct ossification of the mesenchymal tissues. The primitive mesenchymal cells are transformed into osteoprogenitor cells and then into mature osteoblasts leading to the formation of the bone with all of its histological characteristics. This process occurs typically in the calvarial bones, mandible, and the clavicle. In contrast, the epiphysial growth plate in the appendicular skeleton is characterized by the intracartilaginous bone formation. In this process the primitive mesenchymal cells differentiate in a two-step process into mature bone. In the first step, the mesenchymal cells transform into chondroblasts, form collagen and other elements of bone matrix, become ossified, and lead to mature bone. In the embryonic phase a formation of bone through intramembranous compared with intracartilaginous process depends on the anatomical site. As stated earlier, the cranial structures and mandible undergo an intramembranous growth process whereas the appendicular skeleton forms through an intracartilaginous process.
The postfracture healing of bone generally follows in the intracartilaginous ossification process, although with a very high concentration of BMP an intramembranous route may be taken. At this time, it is unclear what factor(s) direct(s) one process (intramembranous, for example) as opposed to the other in the embryonic phase or during fracture healing. Because the bone that is formed as a result of either process is virtually indistinguishable in its final mature form, it is unclear what the biological advantage is of one process over the other.
The cellular and molecular events governing bone formation in the embryo, healing of a fractured bone, and induced bone fusion follow a similar pattern. Discovery, purification, and recombinant synthesis of bone morphogenetic proteins (BMPs) constiute a major milestone in the understanding of bone physiology. In this review the author discusses the mechanism of action, clinical applications, dosage, and optimum carriers for BMPs. The roles played by other growth factors are also discussed.
Bone is unique of all the tissues in the in the vertebrate organism. When injured, it heals by formation of new bone. In contrast, most other tissues such as the heart muscle, voluntary muscles, liver, and the brain heal by replacement of connective tissue rather than the original tissue.
Another interesting attribute of the bone is that the molecular and cellular processes that lead to the development of the skeletal structures within the embryo are very similar to the cascades that occur in the healing process in an injured bone. Likewise, in surgically created fusion, the osseous fusion mass formation recapitulates a fracture healing process, which in turn recapitulates embryonic development of new bone. Thus, there is a common theme in the development of bone from primitive mesenchymal tissues to a well-structured, well-organized histological structure that one associates with mature bone. In addition, the ongoing remodeling process in an adult organism, which is exposed to external physical and hormonal influences, is also modulated through a similar molecular mechanism.
The developing limb bud represents a prototypical example of bone development in the embryo. There is a condensation of primitive mesenchymal cells in the central core of the limb bud, in the area destined to form skeletal structures. This condensation usually transforms into bone through two independent pathways. Intramembranous ossification occurs when there is a direct ossification of the mesenchymal tissues. The primitive mesenchymal cells are transformed into osteoprogenitor cells and then into mature osteoblasts leading to the formation of the bone with all of its histological characteristics. This process occurs typically in the calvarial bones, mandible, and the clavicle. In contrast, the epiphysial growth plate in the appendicular skeleton is characterized by the intracartilaginous bone formation. In this process the primitive mesenchymal cells differentiate in a two-step process into mature bone. In the first step, the mesenchymal cells transform into chondroblasts, form collagen and other elements of bone matrix, become ossified, and lead to mature bone. In the embryonic phase a formation of bone through intramembranous compared with intracartilaginous process depends on the anatomical site. As stated earlier, the cranial structures and mandible undergo an intramembranous growth process whereas the appendicular skeleton forms through an intracartilaginous process.
The postfracture healing of bone generally follows in the intracartilaginous ossification process, although with a very high concentration of BMP an intramembranous route may be taken. At this time, it is unclear what factor(s) direct(s) one process (intramembranous, for example) as opposed to the other in the embryonic phase or during fracture healing. Because the bone that is formed as a result of either process is virtually indistinguishable in its final mature form, it is unclear what the biological advantage is of one process over the other.
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