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B L Foster

Publications and source records attributed to B L Foster.

11 recordsLinked to original sources

Regulation of cementoblast gene expression by inorganic phosphate in vitro.

Examination of mutant and knockout phenotypes with altered phosphate/pyrophosphate distribution has demonstrated that cementum, the mineralized tissue that sheathes the tooth root, is very sensitive to local levels of phosphate and pyrophosphate. The aim of this study was to examine the potential regulation of cementoblast cell behavior by inorganic phosphate (P(i)). Immortalized murine cementoblasts were treated with P(i) in vitro, and effects on gene expression (by quantitative real-time reverse-transcriptase polymerase chain reaction [RT-PCR]) and cell proliferation (by hemacytometer count) were observed. Dose-response (0.1-10 mM) and time-course (1-48 hours) assays were performed, as well as studies including the Na-P(i) uptake inhibitor phosphonoformic acid. Real-time RT-PCR indicated regulation by phosphate of several genes associated with differentiation/mineralization. A dose of 5 mM P(i) upregulated genes including the SIBLING family genes osteopontin (Opn, >300% of control) and dentin matrix protein-1 (Dmp-1, >3,000% of control). Another SIBLING family member, bone sialoprotein (Bsp), was downregulated, as were osteocalcin (Ocn) and type I collagen (Col1). Time-course experiments indicated that these genes responded within 6-24 hours. Time-course experiments also indicated rapid regulation (by 6 hours) of genes concerned with phosphate/pyrophosphate homeostasis, including the mouse progressive ankylosis gene (Ank), plasma cell membrane glycoprotein-1 (Pc-1), tissue nonspecific alkaline phosphatase (Tnap), and the Pit1 Na-P(i) cotransporter. Phosphate effects on cementoblasts were further shown to be uptake-dependent and proliferation-independent. These data suggest regulation by phosphate of multiple genes in cementoblasts in vitro. During formation, phosphate and pyrophosphate may be important regulators of cementoblast functions including maturation and regulation of matrix mineralization.

Animals↗

Extracellular phosphate alters cementoblast gene expression.

Genetic data from humans and mice reveal that the formation of cementum is sensitive to intra- and extracellular phosphate/pyrophosphate distribution. The intracellular molecular pathways whereby altered levels of extracellular phosphate concentration may affect cementum formation have not been elucidated. To initiate inquiry, we have studied the temporal effects of extracellular phosphate on global patterns of gene expression in a line of immortalized mouse cementoblasts. Total RNA from cultured cementoblasts treated with 5 mM inorganic phosphate over a designated time period, from 1-48 hrs, was analyzed for global patterns of gene expression by means of DNA microarrays representing the complete mouse genome. Analyses of significant hybridization signals indicated that 5 mM extracellular phosphate alters the expression of genes comprising several gene ontology (GO) groups, including transcription factor activity and Wnt signaling.

Animals↗

Regulation of cementoblast function by P. gingivalis lipopolysaccharide via TLR2.

Although cementoblasts express Toll-like receptors (TLR)-2 and -4, little is known regarding the possible participation of cementoblasts in the inflammatory response. We investigated the effects of Porphyromonas gingivalis lipopolysaccharide (LPS), tetra- and penta-acylated lipid A species (designated PgLPS(1435/1449) and PgLPS(1690), respectively), on gene expression of osteoclastogenesis-associated molecules in murine cementoblasts. Real-time quantitative RT-PCR analysis revealed that receptor activator of NF-kappaB ligand (RANKL), interleukin-6, Regulated on activation, normal T-cell expressed, and secreted (RANTES), macrophage inflammatory protein-1alpha, and monocyte chemoattractant protein-1 were rapidly and dramatically induced upon stimulation with PgLPS(1690), but only slightly induced with PgLPS(1435/1449). Osteoprotegerin, which was expressed constitutively, was not altered significantly. ELISA demonstrated synthesis of corresponding proteins. PgLPS(1690) significantly induced transcripts for NF-kappaB, and this activation was inhibited by pre-treatment with anti-TLR-2 but not with TLR-4 antibodies. These results suggest that cementoblasts participate in the recruitment of osteoclastic precursor cells by up-regulation of chemokines/cytokines.

Analysis of Variance↗

Regenerating the periodontium: is there a magic formula?

OBJECTIVE: Left untreated, periodontal disease results in destruction of periodontal tissues including cementum, bone and the periodontal ligament, and subsequently, tooth loss. Increased research efforts focused on understanding periodontal disease at the cellular, molecular and clinical level have resulted in improved modalities for arresting disease progression; however, outcomes of existing procedures are not predictable and often disappointing. Critical to improving the predictability of regenerative therapies is targeting studies toward enhancing our understanding of the cellular and molecular events required to restore periodontal tissues. DESIGN: Toward this goal our laboratory has focused on defining cells, mechanisms and factors regulating development of periodontal tissues, using in vitro and in vivo rodent models. RESULTS AND CONCLUSION: Results from these studies have enabled us to identify attractive candidate factors/cells including: 1) products secreted by epithelial cells that act on mesenchymal cells (amelogenins): we observed that both follicle cells and cementoblasts are responsive to amelogenin-like molecules resulting in changes in the expression of genes associated with cell maturation; 2) morphogens (bone morphogenetic proteins, BMP): we report that follicle cells respond differently to BMPs vs. cementoblasts, depending on dose of and specific BMP used; 3) phosphates: existing data suggest that phosphates act as signaling molecules regulating the expression of genes associated with cementoblast maturation. Knowledge gained from these studies has provided insight as to the cells/factors required for designing improved regenerative therapies.

Amelogenin↗

Defining the roots of cementum formation.

Significant progress has been seen in research aimed at regeneration of the disease-damaged periodontium. Our own strategy has been to approach periodontal tissue development (i.e. root, cementum, periodontal ligament, and bone) as a source for the identification of key regulators of cellular processes that may be applicable to periodontal tissue repair. Specifically, enamel-like molecules, bone morphogenetic proteins (BMPs), and phosphates have been investigated for their role in altering gene expression and cell functions in follicle cells, periodontal ligament cells, and cementoblasts. Amelogenin, leucine-rich amelogenin peptide, and tyrosine-rich amelogenin peptide have been found to similarly affect cementoblast gene expression and cementoblast-mediated mineralization in vitro; however, these enamel-like factors do not increase cell proliferation as has been observed in cells treated with Emdogain (Biora AB, Malmö, Sweden), an enamel matrix derivative. BMP-2 has been found to promote differentiation of follicle cells into a cementoblast/osteoblast phenotype, and BMP-3 is being investigated as a negative regulator of mineralization. The increased ratio of phosphate to pyrophosphate in the local region during root development has been found to significantly enhance the extent of cementum formation in animal models. Furthermore, phosphate has been identified as a regulator of cementoblast SIBLING (small integrin-binding ligand N-linked glycoprotein) gene expression in vitro. These investigations of candidate factors for periodontal regeneration have uncovered mechanisms regulating gene expression and cell function in cells controlling the behavior of periodontal tissues (i.e. follicle cells, periodontal cells, and cementoblasts) and offer new directions to consider for clinical repair of periodontal defects.

Animals↗

Cementoblast gene expression is regulated by Porphyromonas gingivalis lipopolysaccharide partially via toll-like receptor-4/MD-2.

Lipopolysaccharides are potent inflammatory mediators considered to contribute to destruction of periodontal tissues. Here, we hypothesized that Porphyromonas gingivalis lipopolysaccharide (P-LPS) treatment would regulate gene expression in murine cementoblasts through Toll-like receptor 4. Real-time (RT)-PCR and Northern blot analysis indicated that P-LPS decreased expression of transcripts for osteocalcin (OCN) and receptor activator of nuclear factor kappaB ligand (RANKL). In contrast, a dose-dependent up-regulation in mRNA levels for osteopontin (OPN) and osteoprotegerin (OPG) was observed. Similarly, ELISA demonstrated decreased RANKL and increased OPG levels. A monoclonal antibody specific for mouse TLR-4/MD-2 partially neutralized the P-LPS effect on cementoblasts. These results indicate that exposure of cementoblasts to P-LPS can alter cell function by regulating markers of osteoclastic activity (e.g., RANKL/OPG), thereby potentially affecting the inflammation-associated resorption of mineralized tissues.

Animals↗

Cementum: a phosphate-sensitive tissue.

Ectopic calcification within joints has been reported in humans and rodents exhibiting mutations in genes that regulate the level of extracellular pyrophosphate, e.g., ank and PC-1; however, periodontal effects of these mutations have not previously been examined. These initial studies using ank and PC-1 mutant mice were done to see if such mineral deposition and resulting ankylosis were occurring in the periodontium as well. Surprisingly, results indicated the absence of ankylosis; however, a marked increase in cementum formation on the root surfaces of fully developed teeth of these mutant mice was noted. Examination of ank mutant mice at earlier ages of tooth root formation indicated that this striking observation is apparent from the onset of cementogenesis. These findings suggest that cells within the periodontal region are highly responsive to changes in phosphate metabolism. This information may prove valuable in attempts to design successful therapies for regenerating periodontal tissues.

Animals↗

Enzymatic hydrolysis of ammonia-treated sugar beet pulp.

Sugar beet pulp is a carbohydrate-rich coproduct generated by the table sugar industry. Beet pulp has shown promise as a feedstock for ethanol production using enzymes to hydrolyze polymeric carbohydrates and engineered bacteria to ferment sugars to ethanol. In this study, sugar beet pulp underwent an ammonia pressurization depressurization (APD) pretreatment in which the pulp was exploded by the sudden evaporation of ammonia in a reactor vessel. APD was found to substantially increase hydrolysis efficiency of the cellulose component, but when hemicellulose- and pectin-degrading enzymes were added, treated pulp hydrolysis was no better than the untreated control.

Ammonia↗

Microdemographic variation and family composition in four Thai villages.

"Examination of Thai ethnographic materials highlights several problems in comparative analysis of social processes that are population linked. Marked differences in family composition among four Central Thai villages are shown to arise primarily from a common family system operating on different underlying sociocultural and demographic processes. Satisfactory analysis requires detailed demographic data, information on other sociocultural processes, and a formal model of family dynamics relating the demographic to the other kinds of data. Lack of even one of these three components may make comparison meaningless. Demographic anthropology and historical demography provide complementary data well suited to anthropological studies of social organization."

Anthropology, Cultural↗