The potential role of bone morphogenetic proteins in periodontal reconstruction.

Growth factors and cytokines are currently under investigation as potential therapeutics for the site-specific regeneration of alveolar bone. Many of these factors, including TGF-beta, PDGF, IGF-I, IGF-II, and FGF influence bone growth and resorption, and as such may be useful in the regeneration process. However, these molecules have effects on many other tissue and cell types. In contrast, the bone morphogenetic proteins (BMPs) represent a unique set of differentiation factors that induce new bone formation at the site of implantation instead of changing the growth rate of pre-existing bone. Recombinant human BMP-2 (rhBMP-2), for example, has been shown to induce ectopic bone formation in an in vivo setting. Cell culture studies indicate that rhBMP-2 can cause mesenchymal precursor cells to differentiate into cartilage- and bone-forming cells. Additional animal studies have shown that rhBMP-2 is capable of replacing large (2.5 cm) defects in canine mandibles, healing a variety of long bone defects in orthopedic animal models, and repairing bony defects in animal models of bone lost due to periodontal disease. These results suggest that rhBMP-2 has broad therapeutic potential for dental and cranio/maxillofacial reconstruction.

[1]  U. Wikesjö,et al.  Periodontal regenerative potential of space-providing expanded polytetrafluoroethylene membranes and recombinant human bone morphogenetic proteins. , 1995, Journal of periodontology.

[2]  P. Schnegelsberg,et al.  Osteogenic protein-2. A new member of the transforming growth factor-beta superfamily expressed early in embryogenesis. , 1992, The Journal of biological chemistry.

[3]  V. Rosen,et al.  The healing of segmental bone defects, induced by recombinant human bone morphogenetic protein (rhBMP-2). A radiographic, histological, and biomechanical study in rats. , 1992, The Journal of bone and joint surgery. American volume.

[4]  A. Yamaguchi,et al.  BMP-2 induces differentiation of a non-osteogenic fibroblasatic cell line (C3H10T1/2) into both osteoblatsts and chondroblasts in vitro , 1992 .

[5]  E. Wang,et al.  Mandibular reconstruction with a recombinant bone-inducing factor. Functional, histologic, and biomechanical evaluation. , 1991, Archives of otolaryngology--head & neck surgery.

[6]  E. Canalis,et al.  Transforming growth factor-beta and remodeling of bone. , 1991, The Journal of bone and joint surgery. American volume.

[7]  A. Reddi,et al.  Stimulation of chondrogenesis in limb bud mesoderm cells by recombinant human bone morphogenetic protein 2B (BMP-2B) and modulation by transforming growth factor beta 1 and beta 2. , 1991, Experimental cell research.

[8]  V. Rosen,et al.  Recombinant human bone morphogenetic protein-2 stimulates osteoblastic maturation and inhibits myogenic differentiation in vitro , 1991, The Journal of cell biology.

[9]  F. Luyten,et al.  Osteogenin promotes reexpression of cartilage phenotype by dedifferentiated articular chondrocytes in serum-free medium. , 1991, Experimental cell research.

[10]  V. Rosen,et al.  Identification of transforming growth factor beta family members present in bone-inductive protein purified from bovine bone. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[11]  H. Oppermann,et al.  Bovine osteogenic protein is composed of dimers of OP-1 and BMP-2A, two members of the transforming growth factor-beta superfamily. , 1990, The Journal of biological chemistry.

[12]  E. Drier,et al.  OP‐1 cDNA encodes an osteogenic protein in the TGF‐beta family. , 1990, The EMBO journal.

[13]  V. Rosen,et al.  Recombinant human bone morphogenetic protein induces bone formation. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[14]  F. Luyten,et al.  Stimulation of the expression of osteogenic and chondrogenic phenotypes in vitro by osteogenin. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[15]  L. Bonewald,et al.  Activation of the bone-derived latent TGF beta complex by isolated osteoclasts. , 1989, Biochemical and biophysical research communications.

[16]  V. Rosen,et al.  Novel regulators of bone formation: molecular clones and activities. , 1988, Science.

[17]  V. Rosen,et al.  Purification and characterization of other distinct bone-inducing factors. , 1988, Proceedings of the National Academy of Sciences of the United States of America.

[18]  E. Canalis,et al.  Transforming growth factor beta is a bifunctional regulator of replication and collagen synthesis in osteoblast-enriched cell cultures from fetal rat bone. , 1987, The Journal of biological chemistry.

[19]  A. Reddi,et al.  Dissociative extraction and reconstitution of extracellular matrix components involved in local bone differentiation. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[20]  M. Urist,et al.  Bone morphogenesis in implants of insoluble bone gelatin. , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[21]  M. Urist,et al.  Bone: Formation by Autoinduction , 1965, Science.

[22]  E. Wang,et al.  Bone morphogenetic protein-2 causes commitment and differentiation in C3H10T1/2 and 3T3 cells. , 1993, Growth factors.

[23]  E. Canalis,et al.  Transforming Growth Factor-β Stimulates Bone Matrix Apposition and Bone Cell Replication in Cultured Fetal Rat Calvariae* , 1990 .

[24]  L. Bonewald,et al.  Role of transforming growth factor-beta in bone remodeling. , 1990, Clinical orthopaedics and related research.

[25]  J. Lian,et al.  Effects of bone associated growth factors on DNA, collagen and osteocalcin synthesis in cultured fetal rat calvariae. , 1988, Bone.