Biography

Research Interests

Bone formation is a complex developmental process involving the initial recruitment and differentiation of mesenchymal stem cells to chondrocytes and osteoblasts, cells that produce cartilage and bone. Our laboratory studies signals regulating the differentiation and functioning of osteoblasts. Current research projects are addressing the following areas:

Transcriptional Control of Osteoblast Differentiation: The goal of this work is to identify specific DNA sequences and associated transcription factors responsible for the activation of the osteoblast-related genes encoding osteocalcin and bone sialoprotein, and to understand how these genes are regulated by hormonal and extracellular matrix signals. Both these proteins exhibit a bone-restricted pattern of expression and play fundamental roles in bone formation. Particular interest is focused on the importance of cell:extracellular matrix interactions which are known to activate osteoblast-specific gene expression via an integrin-mediated pathway possibly involving the phosphorylation of specific transcription factors.

Role of Bone Matrix Proteins in Biomineralization: We have defined an osteoblast cell culture system that forms a highly mineralized bone-like extracellular matrix in vitro. To test the function of specific bone matrix proteins in the mineralization process, antisense RNA and forced expression approaches are being used to disrupt or stimulate the synthesis of specific proteins and examine effects on biomineralization.

Use of Adenovirus Vectors in Gene Therapies for Bones and Teeth. We have developed adenovirus vectors capable of expressing cDNAs for several important molecules such as the bone morphogenetic proteins which are involved in bone and tooth regeneration. A viral vector expressing BMP7 was recently shown to stimulate bone formation after application to a soft tissue site. This gene therapy approach may be useful for stimulating the regeneration of long bones, craniofacial structures, and the dentin and cementum of teeth.

Selected Publications

Benson MD, Bargeon JL, Xiao G, Cui Y and Franceschi RT.Identification of a homeodomain binding element in the bone sialoprotein promoter which is required for its osteoblast-selective expression. J Biol Chem 275:13907-13917, 2000

Xiao G, Jian D, Thomas P, Benson MD, Guan K, Karsenty G and Franceschi RT. MAPK pathways activate and phosphorylate the osteoblast-specific transcription factor, Cbfa1. J Biol Chem, 275:4453-4459, 2000.

Franceschi RT, Wang D, Krebsbach PH and Rutherford RB. Gene therapy for bone formation: in vitro and in vivo osteogenic activity of an adenovirus expressing BMP7. J Cell Biochem 78:476-486,2000.

Franceschi, R.T. (1999) The Developmental control of osteoblasts-specific gene expression: Role of specific transcription factors and the extracellular matrix environment. Crit. Rev. Oral Biol. Med. 10:40-57.

Lab Personnel

From Left to Right: Shuying Yang, Ph.D. shuyingy@umich.edu Di Jiang, D.D.S., M.S. djiang@umich.edu Dian Wang, M.S. wangzhe@umich.edu Raj Gopalakrishnan, D.D.S., Ph.D. rgopalak@umich.edu Guozhi Xiao, M.D., Ph.D. xiaogz@umich.edu June Phimphilai, M.D. mphimphi@umich.edu Renny Franceschi, Ph.D. rennyf@umich.edu