The potential role of bone morphogenic proteins in periodontal reconstruction
Bone matrix is known to contain a great number of growth factors. Some of these are fibroblast growth factor (FGF), insulin-like growth factor I and II (GIF), transforming growth factor beta (TGF-B), platelet-derived growth factors (PDGF), and bone morphogenic proteins (BMPs).The latter have been shown to have the ability to induce cartilage and bone formation when implanted ectopically into an animal. BMP proteins have a structural characteristic of a hydrophobic secretory leader sequence, a large propeptide region, and a mature domain. The mature domain contains the active component of the molecule. BMPs are dimeric, glycosylated proteins. Upon secretion, a cleavage event occurs such that the mature, active protein that results is a dimer of the carboxy-terminal region of the precursor peptide. BMPs combined with a carrier matrix have been implanted in rats. They have demonstrated the ability to induce the complete sequence of endochondral ossification resulting in the local induction of cartilage tissue which is removed and replaced by bone and bone marrow. BMP reduces the time needed for bone formation to occur. Researchers think that BMP may influence the direct bone formation pathway as well as the endochondral sequence. It has been observed that rh-BMP-2 has successfully healed segmental defects in femurs of rat and sheep, mandibles of dogs, and skull defects in rats and dogs: rh-BMP-2 was implanted with a collagenous bone matrix carrier; the carrier was used as the control. Bone formation was first observed at one month in the rh-BMP-treated animals, increasing in density at three and six months. BMPs have been demonstrated to affect differentiation of cells into the chondrocyte lineage. BMPs also have been shown to directly differentiate cells into cells of the osteoblast phenotype. BMPs are the only known factors that will reduce expression of osteocalcin, the most specific marker of the mature osteoblast.TGF-B, IGF and FGFs all affect the already differentiated bone-forming cells, causing them to divide or increase secretion of extracellular matrix. On the other hand, rh-BMP-2 will affect the precursor cells, cells from the bone marrow environment, and the soft tissue surrounding the defect area and differentiate into cartilage and bone cells. Therefore, the proximity of the bone is less of a factor in the regeneration. These findings suggest that BMP has a broad therapeutic potential for dental and cranio-maxillofacial reconstruction. [M.C.R.]
Wozney, J.M., J Periodont,66:506,1995