title: Mechanisms of osteoinduction/chondroinduction by demineralized bone.
abstract: Demineralized bone is widely used for osseous reconstructive procedures. Bone morphogenetic proteins (BMPs) have been studied as the putative active components of demineralized bone; recombinant BMPs are Food and Drug Administration-approved for use with scaffold carriers. An experimental three-dimensional in vitro model was developed to allow comparison of early changes in signaling and gene expression in cells exposed to demineralized bone particles (DBPs) or to BMP and/or transforming growth factor beta (TGF-beta). The culture device consists of a bilayer of porous collagen lattice that contains either a packet of DBPs or an insert of the dense collagen scaffold with BMP and/or TGF-beta. As expected, BMP and TGF-beta induced distinct signaling pathways and events in human dermal fibroblasts; DBPs signaled both pathways and their target genes. A mixture of BMP and TGF-beta stimulated the production of extracellular matrix chondroitin that approximated the composition that was stimulated by DBPs, but to a lesser amount. Although BMP was originally isolated as the active factor in DBPs, it does not show DBPs' effects on signaling and chondroinduction in vitro. Multiple members of the TGF-beta superfamily and other constituent factors may be involved in skeletal induction of human dermal fibroblasts by DBPs. This in vitro culture system may be useful to provide a rational basis for designing improved osteoinductive/chondroinductive materials.
authors.affiliation: Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA. jglowacki@rics.bwh.harvard.edu
authors.forename: Julie
authors.initials: J
authors.lastname: Glowacki
authors.forename: Shuanhu
authors.initials: S
authors.lastname: Zhou
authors.forename: Shuichi
authors.initials: S
authors.lastname: Mizuno
mesh_terms: D001857:Bone Matrix / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology*; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000187:drug effects / Q000235:genetics*; D002807:Chondroitin / Q000096:biosynthesis; D003094:Collagen; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005347:Fibroblasts; D015870:Gene Expression; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics; D010012:Osteogenesis / Q000187:drug effects / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D054457:Tissue Scaffolds; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000494:pharmacology*; D000099222:betaIG-H3 Protein
chemical_list: D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D002807:Chondroitin; D003094:Collagen; D016326:Extracellular Matrix Proteins; D018972:Insulin-Like Growth Factor Binding Protein 3; D018969:Insulin-Like Growth Factor Binding Proteins; D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C515497:IGFBP3 protein, human; C051321:SERPINE1 protein, human; C499469:recombinant human bone morphogenetic protein-2