EXPRESSION AND ROLES OF CCN2 DURING ODONTOGENESIS
Odontogenesis is a complex, multi-stage and fundamental process that involves epithelial-mesenchymal interactions, polarized growth, morphogenesis and differentiation of ameloblasts and odontoblasts. Studies have shown that these complex developmental events require continuous and reiterative action by signaling molecules at successive stages and multiple sites. However, the exact nature of these factors, the steps controlled by them, and the means by which they exert their roles at multiple sites and times are not fully known. Our recent work described here shows for the first time that CCN2/connective tissue growth factor (CTGF), a member of the powerful CCN effector family, is involved in, and regulates, odontogenesis. CCN2 is first expressed at the onset of odontogenesis along with transforming growth factor β1(TGF-β1) and bone morphogenetic proteins 2 and 4 (BMP-2 and BMP-4), characterizes enamel knot and preameloblasts in conjunction with Sonic hedgehog (SHH) at subsequent stages, and then persists in differentiating and mature odontoblasts. CCN2 gene expression increases during differentiation of dental precursor cells in culture, and exogenous BMPs stimulate CCN2 expression in tooth germs explants. Exogenous recombinant CCN2 (rCCN2) stimulates proliferation in dental epithelium and mesenchyme. Interference with CCN2 action by neutralizing antibodies, however, inhibits cell proliferation and ameloblast and odontoblast differentiation. The results show that CCN2 is a powerful and developmentally controlled signaling molecules during tooth development, and has previously unsuspected roles such as stimulation of proliferation and promoting maturation in odontogenic cells. In this chapter, our previous studies are summarized and new data are presented. Taken together, our data demonstrate for the first time that CCN2 is expressed during, and regulates, odontogenesis. CCN2 expression is confined to specific sites and times in the developing tooth germ, is regulated by TGF-β and BMPs, and appears to be necessary for normal growth and cytodifferentiation of ameloblasts and odontoblasts.
