Tissues lost as a consequence of periodontal diseases, i.e. bone, cementum
and a functional periodontal ligament (PDL), can be restored to some degree
. Nevertheless, results are often disappointing. There is a need to develop
new paradigms for regenerating periodontal tissues that are based on an un
derstanding of the cellular and molecular mechanisms regulating the develop
ment and regeneration of periodontal tissues. As one approach we have devel
oped strategies for maintaining cementoblasts in culture by first determini
ng the gene profile for these cells in situ. Next, cells were immortalized
in vitro using SV 40 large T antigen (SV40 Tag) or by using mice containing
transgenes enabling cellular immortality ill vitro. Cementoblasts in vitro
retained expression of genes associated with mineralized tissues, bone sia
loprotein and osteocalcin, that were not linked with periodontal fibroblast
s either in situ or in vitro. Further, cementoblasts promoted mineralizatio
n in vitro as measured by von Kossa and ex vivo using a severely compromise
d immunodeficient (SCID) mouse model. These cells responded to growth facto
rs by eliciting changes in gene profile and mitogenesis and to osteotropic
hormones by evoking changes in gene profile and ability to induce mineral n
odule formation in vitro. The ultimate goal of these studies is to provide
the knowledge base required for designing improved modalities for use in pe
riodontal regenerative therapies.