title: Bone formation by BMP-7-transduced human gingival keratinocytes.
abstract: BMPs are a family of pleiotropic signaling molecules involved at various stages in the formation of bones and teeth. In addition, recombinant BMP can induce bone and dentin regeneration when applied directly to adult tissues. We have shown that fibroblasts transduced ex vivo by BMP cDNA delivered by recombinant adenoviruses induce bone formation and convert to osteoblasts upon implantation in vivo. To determine if this osteogenic capacity was limited to fibroblasts, we found that BMP-7-transduced human oral keratinocyte cells (HOKC) also formed ectopic bone. The ossicles formed by the BMP-7-transduced HOKC were smaller and more dense than those formed by BMP-7-transduced human gingival fibroblasts (HGF). Implanted HOKC were localized adjacent to the developing bone by immunocytochemical detection of keratin expression. However, no bone-like tissue formed when HOKC were implanted into diffusion chambers in vivo. We conclude that BMP-transduced HOKC secrete BMP and form bone in vivo but, unlike BMP-transduced HGF, do not transdifferentiate to osteoblasts.
authors.affiliation: Center for Biorestoration of Oral Health, School of Dentistry, University of Michigan, 1011 N. University, Ann Arbor, MI 48109-1078, USA rbruth@umich.edu.
authors.forename: R B
authors.initials: RB
authors.lastname: Rutherford
authors.forename: P
authors.initials: P
authors.lastname: Racenis
authors.forename: S
authors.initials: S
authors.lastname: Fatherazi
authors.forename: K
authors.initials: K
authors.lastname: Izutsu
mesh_terms: D000328:Adult; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D015194:Diffusion Chambers, Culture; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005881:Gingiva / Q000166:cytology*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects*; D010006:Osteoblasts / Q000166:cytology; D010012:Osteogenesis / Q000187:drug effects*; D011994:Recombinant Proteins / Q000494:pharmacology; D014161:Transduction, Genetic; D016212:Transforming Growth Factor beta
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta