Regulation of Osteoprotegerin Gene Expression in Dental Follicle Cells

Abstract

Colony-stimulating factor-one (CSF-1) and parathyroid-hormone-related protein (PTHrP) down-regulate osteoprotegerin (OPG) gene expression in the dental follicle of the rat first mandibular molar. To examine this regulation at the signal transduction level, we treated cultured dental follicle cells with either phorbolmyristate acetate (PMA) or dibutyryl cyclic AMP (dbcAMP) to activate either protein kinase C (PKC) or protein kinase A (PKA). Our results demonstrate that PMA up-regulates OPG gene expression and down-regulates the expression of CSF-1 and the PTHrP receptor (PTHrP-R). Conversely, dbcAMP down-regulates OPG expression and up-regulates CSF-1 and PTHrP-R expression. Immunostaining shows that PMA also increases the steady-state levels of protein. Thus, treatment with agents that affect protein kinase activity also enhance the steady-state mRNA and protein levels of OPG, as well as decreasing the mRNA levels of CSF-1 and PTHrP-R. The PKC-alpha isoform may be critical in OPG regulation because PKC-alpha gene expression is enhanced by PMA and reduced by either CSF-1 or PTHrP.

HSP25 Affects the Proliferation and Differentiation of Rat Dental Follicle Cells

“…Similarly, in the present study, murine recombinant HSP25 directly enhanced the ALP activity of DFCs, in accordance with results from other studies that indicated that HSP25 could be induced in osteoblasts via protein kinase C (PKC), mitogen-activated protein kinases (MAPK), and phosphatidylinositol 3-kinase (PI3K) /protein kinase B (Akt) (Kozawa et al, 2001;Tokuda et al, 2002;Hatakeyama et al, 2002;Takai et al, 2006). Moreover, PKC gene elevation may be critical to OPG regulation in DFCs (Wise et al, 2003), and VEGF, BMP2 and BMP7 may lead DFCs to a cementoblast/osteoblast pathway through MAPK involvement (Chen et al, 2007;Kémoun et al, 2007). Thus, in the future, we will investigate further whether HSP25 regulates ALP activity through PKC, MAPK or the PI3K/Akt pathway.…”

Injections of osteoprotegerin and PMA delay tooth eruption

“…In vitro, PMA enhances the expression of PKC in the dental follicle cells, particularly PKC-a (Wise et al, 2003). In vivo, PKC-a expression is reduced at Day 3 , and this correlates with the decrease in OPG expression at Day 3.…”

“…We have hypothesized that this drop would allow osteoclastogenesis to occur for eruption (Wise et al, 2000(Wise et al, , 2002b, particularly because this is combined with the maximal expression of CSF-1 at this time . At the signal transduction level, enhancement of the gene expression and activation of protein kinase C (PKC) by PMA upregulates the expression of OPG in the dental follicle (Wise et al, 2003). In vitro, PMA enhances PKC-a and OPG expression in follicle cells, suggesting that elevation of PKC-a would enhance OPG gene expression (Wise et al, 2003).…”

“…At the signal transduction level, enhancement of the gene expression and activation of protein kinase C (PKC) by PMA upregulates the expression of OPG in the dental follicle (Wise et al, 2003). In vitro, PMA enhances PKC-a and OPG expression in follicle cells, suggesting that elevation of PKC-a would enhance OPG gene expression (Wise et al, 2003). This is supported by correlative in vivo studies showing that PKC-a is reduced at Day 3 at the time when OPG gene expression is reduced .…”

“…In conjunction with this, a related aim was to determine if injection of phorbolmyristate acetate (PMA), an activator of PKC and an enhancer of OPG gene expression (Wise et al, 2003), would delay tooth eruption. PMA was only injected in the early postnatal days (Days 1-4) such that OPG expression, as well as PKC-a expression, would be enhanced.…”