title: Inductive activity of recombinant human growth and differentiation factor-5.
abstract: Growth and differentiation factor-5 (GDF-5) is a divergent member of the transforming growth factor-beta/bone morphogenetic protein (BMP) superfamily that is required for proper skeletal patterning and development in the vertebrate limb. Based on the homology of GDF-5 with other bone-inducing BMP family members, the inductive activity of a recombinant form of human GDF-5 (rhGDF-5) was evaluated in a series of in vitro assays and in vivo bone-formation models. The in vitro response to rhGDF-5 resulted in the formation of chondrogenic nodules in fetal rat calvarial cells cultured in the context of collagen or collagen/hyaluronate extracellular matrices. Matrices loaded with rhGDF-5 induced ectopic cartilaginous and osseous tissue when implanted in subcutaneous or intramuscular sites. In non-human primate long-bone-defect and spinal-fusion models, rhGDF-5 combined with a mineralized collagen matrix induced bone formation in a manner equivalent to autogenous bone. These results highlight the unique potential of rhGDF-5 in a wide variety of orthopaedic applications.
authors.affiliation: Orquest, Inc., 365 Ravendale Drive, Mountain View, CA 94043, USA. bspiro@orquest.com
authors.forename: R C
authors.initials: RC
authors.lastname: Spiro
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.forename: M A
authors.initials: MA
authors.lastname: Heidaran
authors.forename: A Y
authors.initials: AY
authors.lastname: Thompson
authors.forename: C K
authors.initials: CK
authors.lastname: Ng
authors.forename: J
authors.initials: J
authors.lastname: Pohl
authors.forename: J W
authors.initials: JW
authors.lastname: Poser
mesh_terms: D020341:Absorbable Implants; D000818:Animals; D001846:Bone Development; D019485:Bone Morphogenetic Proteins; D016025:Bone Transplantation / Q000379:methods; D002417:Cattle; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism / Q000627:therapeutic use; D005260:Female; D055428:Growth Differentiation Factor 5; D006133:Growth Substances / Q000378:metabolism* / Q000502:physiology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D010215:Papio; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000378:metabolism* / Q000627:therapeutic use; D013131:Spine / Q000000981:diagnostic imaging; D013997:Time Factors
chemical_list: D019485:Bone Morphogenetic Proteins; C525893:GDF5 protein, human; D055428:Growth Differentiation Factor 5; D006133:Growth Substances; D011994:Recombinant Proteins; D003094:Collagen