title: Early events: the in vitro conversion of BMP transduced fibroblasts to chondroblasts.
abstract: Strategies for localized skeletal regeneration using either cell or ex vivo gene transfer typically utilize preosteoblasts from bone or bone marrow biopsies. Our studies have demonstrated than ex vivo bone morphogenetic proteins (BMP) transduced fibroblasts convert to osteoblasts and form bone in vivo. In addition when suspended in a variety of thermoset hydrogels, these cells are capable of ectopic or orthotopic bone formation. To study the mechanism of the phenotypic conversion of BMP transduced fibroblasts, we have initiated characterization of three-dimensional (3D) cultures derived from these cell/collagen hydrogel composites. These data reveal that the BMP, but not control transduced fibroblasts, secrete BMP-7 and acquire some chondroblastic traits in 3D cultures. These traits include altered cell shape and changes in the extracellular matrix such as accumulation of cartilage proteoglycan, type II collagen, and mineral deposition by 3 weeks. These studies suggest that this culture system may be useful for elucidating early mechanistic events in the BMP-induced conversion of fibroblasts to osteoblasts.
authors.affiliation: School of Dentistry and The Center for Biorestoration of Oral Health, University of Michigan, Ann Arbor, Michigan 48109-1078, USA. rbruth@umich.edu
authors.forename: R Bruce
authors.initials: RB
authors.lastname: Rutherford
authors.forename: Keni
authors.initials: K
authors.lastname: Gu
authors.forename: Pat
authors.initials: P
authors.lastname: Racenis
authors.forename: Paul H
authors.initials: PH
authors.lastname: Krebsbach
mesh_terms: D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins / Q000235:genetics* / Q000378:metabolism; D002113:Calcification, Physiologic / Q000502:physiology; D019902:Chondrocytes / Q000166:cytology* / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology* / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D018874:Spheroids, Cellular / Q000378:metabolism; D014161:Transduction, Genetic; D014170:Transformation, Genetic; D016212:Transforming Growth Factor beta
chemical_list: C525819:BMP7 protein, human; D055419:Bone Morphogenetic Protein 7; D019485:Bone Morphogenetic Proteins; D016212:Transforming Growth Factor beta