The role of recombinant human bone morphogenetic protein-2 in PLGA capsules at an extraskeletal site of the rat.

Bone morphogenetic protein-2 (BMP-2) is a member of the transforming growth factor-beta (TGF-beta) superfamily and has strong bone-inductive activity in vivo. To examine the role of BMP-2 in an extraskeletal site of rat using a controlled release system of peptides, we encapsulated the recombinant human BMP-2 (rhBMP-2) with poly(DL-lactide-co-glycolide) (PLGA) and implanted the rhBMP-2/PLGA capsules in the subcutaneous area of rats. Upon histochemical examination, it was found that bone-inducing cells having alkaline phosphatase (ALP) activity appeared around the capsules by the suitably released rhBMP-2. In addition, the temporal histological examination showed that direct bone formation without cartilage occurred in the process of this ectopic bone induction. These data indicate that the role of rhBMP-2 in the extraskeletal site of rats is to induce the differentiation of mesenchymal cells into the osteoblasts.

[1]  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.

[2]  V. Rosen,et al.  Recombinant human bone morphogenetic protein-2 induces osteoblastic differentiation in W-20-17 stromal cells. , 1992, Endocrinology.

[3]  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.

[4]  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.

[5]  K. Ishihara,et al.  Bone morphogenetic protein encapsulated with a biodegradable and biocompatible polymer. , 1996, Journal of biomedical materials research.

[6]  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.

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

[8]  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.

[9]  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.

[10]  C. Tickle,et al.  Bone morphogenetic protein-2 (BMP-2) inhibits muscle development and promotes cartilage formation in chick limb bud cultures. , 1996, Developmental biology.

[11]  M. Klagsbrun,et al.  Growth factors in bone matrix. Isolation of multiple types by affinity chromatography on heparin-Sepharose. , 1986, 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]  M. Urist.  Bone: Formation by Autoinduction , 1965, Science.

[14]  K. Ishihara,et al.  Ectopic induction of cartilage and bone by bovine bone morphogenetic protein using a biodegradable polymeric reservoir. , 1996, Journal of biomedical materials research.

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

[16]  E. Pişkin,et al.  Biodegradable polymers as biomaterials. , 1995, Journal of biomaterials science. Polymer edition.

[17]  J. Wozney,et al.  Poly(α-hydroxy acid) carrier for delivering recombinant human bone morphogenetic protein-2 for bone regeneration , 1996 .

[18]  K. L. Miller,et al.  Bovine bone activin enhances bone morphogenetic protein-induced ectopic bone formation. , 1992, The Journal of biological chemistry.

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