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Bone Formation by BMP-7-transduced Human Gingival Keratinocytes

Center for Biorestoration of Oral Health, School of Dentistry, University of Michigan, 1011 N. University, Ann Arbor, MI 48109-1078; and
¹ Department of Oral Biology, School of Dentistry, University of Washington;

*corresponding author, rbruth{at}umich.edu

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.

KEY WORDS: bone morphogenetic protein-7 • keratinocytes • bone formation • gene therapy • cell differentiation