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Extracellular phosphate (Pi) has been shown to act as a signaling molecule capable of altering gene expression and cellular function during osteoblastic differentiation. In this study, we investigated whether Pi regulates expression of bone morphogenetic protein (BMP)-2, a crucial regulator of osteogenic differentiation, and explored the signaling pathway involved using human dental pulp cells and human periodontal ligament cells. We found that Pi increased BMP-2 gene expression. Experiments using signaling inhibitors revealed that the increase in BMP-2 expression was dependent on the cAMP/protein kinase A signaling pathway. We also showed that Pi activates the ERK1/2, and treatment with PD98059, an ERK1/2 inhibitor, suppressed Pi-mediated BMP-2 increase, indicating that activation of the ERK1/2 pathway is required for this Pi-mediated response. These findings demonstrate a novel ability of Pi to stimulate BMP-2 via cAMP/protein kinase A and ERK1/2 pathways. more...

Wnt signaling has been implicated in increased bone formation by controlling mesenchymal stem cell or osteoblastic cell functions; however the role of Wnt signaling on cementogenesis has not been examined. Exposure to Wnt3a inhibited the expression of the osteocalcin (OCN) gene. This effect was accompanied by decreased gene expression of Runx2. Pretreatment with Dickkopf-1 attenuated the suppressive effects of Wnt3a on mRNA expression of Runx2 and OCN on cementoblasts. These findings suggest that canonical Wnt signaling inhibits cementoblast differentiation via regulation of expression of Runx2. Elucidating the role of Wnt in controlling cementoblast function will provide new tools needed to improve on existing periodontal regeneration therapies. more...

We investigated the mechanism and impact of various inflammatory stimuli on dendritic cell (DC)-gingival fibroblast (GF) adhesion. Human immature (im) DCs were generated from monocytes by culturing with interleukin (IL)-4 and granulocyte macrophage-colony stimulating factor (GM-CSF). GFs were outgrown from the human gingival specimen. DCs were co-cultured with GFs with/without pretreatment with various stimuli. Adhered cells were measured by fluorometer. Expression of adhesion molecules was analyzed by flow cytometry. Pretreatment of GFs with tumor necrosis factor (TNF)-α, interferon (IFN)-γ, and Escherichia coli (Ec) lipopolysaccharides (LPS) significantly increased the adhesion to imDCs and enhanced intercellular adhesion molecule (ICAM)-1 expression. A signifi-cantly increased DC-GF adhesion was also observed when imDCs were pretreated with Ec LPS, Porphyromonas gingivalis (Pg) fimbriae, and peptideglycan but not with Pg LPS. Expression of LFA-1 and Mac-1 on DCs was not altered by the pretreatment with these stimuli. However, LFA-1 and Mac-1 blockade of imDC signifi cantly reduced the adhesion to TNF-α-stimulated GFs. These results showed that inflammatory stimuli increased the imDC-GF adhesion via lymphocyte function- associated antigen (LFA)-1/Mac-1-ICAM-1 ligation. Adhesion of DC to GFs may be important not only for the localization of DCs in the inflammatory periodontal lesion, but also for the modulation of immune responses. more...