Fibroblasts regulate differently cell proliferation and differentiation according to origins

Objectives: The aim of this study was to verify the hypothesis that human periodontal ligament fibroblasts (PLF) induce osteogenic differentiation of embryonic stem (ES) cells more than gingival fibroblasts (GF) and this effect is related to the different patterns in producing fibroblast growth factors (FGFs). Methods: This study examined the abilities of the three fibroblast populations including PLF, GF and skin fibroblasts (SF) in stimulating proliferation and osteoblastic differentiation of ES cells in co-cultures. This study also determined the levels of FGFs, transforming growth factors, and bone morphogenic proteins produced by the fibroblasts themselves. In addition, the regulatory role of FGF7 on the proliferation and osteoblastic differentiation is investigated. Results: PLF stimulated sensitively the proliferation of ES cells more than GF or SF in a growing medium, whereas this was inhibited by the addition of DAG (100 nM dexamethasone, 50 uM ascorbic acid, 5 mM beta-glycerophosphate). All the fibroblasts tested induced osteoblastic differentiation of ES cells in co-cultures and this was significantly augmented in the presence of DAG. This induction was proportional to the ability to produce FGF7 of the cells, where PLF secreted FGF7 more than GF and SF. Especially, exogenous addition of recombinant FGF7 augmented Runx2 expression and ALP activity, and the effects of FGF7 were prevented either by treating its specific antibody or by adding c-Jun N-terminal kinase inhibitor. Conclusion: PLF could regulate more sensitively the proliferation and osteoblastic differentiation of embryonic stem cells than GF and SF via the secretion of FGF7, where JNK-mediated signaling is involved.