Biomedical subjects

Brian L Foster

Publications and source records attributed to Brian L Foster.

5 recordsLinked to original sources

PubMed2006

Amelogenins regulate expression of genes associated with cementoblasts in vitro.

Amelogenins are major proteins expressed by ameloblasts during development of the crown (enamel and dentin). These matrix proteins guide crystal habits of the mineral phase of developing enamel and are possible regulators of other genes/proteins during development and maturation of crown and root (dentin and cementum). This study focused on defining the effect that a specific proteolytic cleavage product of amelogenin, tyrosine-rich amelogenin peptide (TRAP), has on cementoblast behavior. Immortalized cementoblasts (OCCM-30) were exposed to TRAP in vitro. Cells treated with TRAP were evaluated for cell proliferation, gene expression for osteocalcin (OCN), osteopontin (OPN), and bone sialoprotein (BSP), and induction of mineral nodule formation. No significant difference in cell proliferation was found between vehicle-treated cells and those treated with TRAP for up to 9 d after treatment. Gene expression of OCN, OPN, and BSP in TRAP-treated cementoblasts showed down-regulation, up-regulation, and no significant change, respectively, relative to vehicle control. A marked decrease in mineral nodule formation was found in cells treated with TRAP compared with the vehicle control, in a dose-dependent manner. These data, along with our previous results demonstrating similar activity with full-length amelogenin and leucine-rich amelogenin peptide (LRAP), suggest that amelogenin-like molecules regulate mesenchymal cell behavior.

Amelogenin↗

PubMed2005

Bisphosphonate modulates cementoblast behavior in vitro.

BACKGROUND: Cementum formation is deemed to be instrumental for the successful regeneration of periodontal tissues, and thus events and modifiers of cementum formation and mineralization need to be determined. This study aimed to determine whether the bisphosphonate 1-hydroxyethylidene-1,1-bisphosphonate (HEBP) altered the behavior of immortalized cementoblasts (osteocalcin-cementoblasts [OCCM]). METHODS: OCCM from transgenic mice were exposed to HEBP at concentrations ranging from 0.01 to 10.0 microM. The assays performed included the count of cell number for proliferation, Northern blot analysis for gene expression (up to 10 days for core binding factor alpha-1 [Cbfa1], bone sialoprotein [BSP], osteocalcin [OCN], and osteopontin [OPN], markers for cementoblast/osteoblast maturation/mineralization), von Kossa stain and alizarin red S stain for mineralization, and enzyme assay (p-nitrophenol phosphate cleavage) for alkaline phosphatase (ALP) activity. RESULTS: Mineral nodule formation was inhibited at the higher doses of HEBP (1.0 and 10.0 microM) only. At early stages (1, 3, and 6 days), gene expression assays revealed only subtle changes in treated cells versus untreated cells, but by day 10, groups treated with lower doses (0.01 and 0.1 microM) were markedly different at the gene expression level. OCN was significantly downregulated (70%) at the lowest dose, with less pronounced effects at higher doses. In concurrence, the master switch gene for osteoblasts, Cbfa1, was also downregulated at the lower doses. Inversely, OPN mRNA was enhanced at the lower doses. ALP activity was not altered by HEBP. CONCLUSION: Bisphosphonate alters cementoblast function in vitro through the regulation of gene expression and mineral formation.

Alkaline Phosphatase↗

PubMed2005

The crowning achievement: getting to the root of the problem.

An ideal goal of oral-craniofacial dental reconstructive therapy is to establish treatment modalities that predictably restore functional tissues. One major area of focus has been in the area of dental materials with marked improvements in the design of materials used to restore teeth/periodontium/bone lost as a consequence of disease or disorders. With advances in understanding the cell and molecular controls for development and regeneration of tooth structures, it is now possible to consider therapies that promote regeneration of lost tissues, along with replacement of these tissues. This review presents a background on our current knowledge as to the composition of the tooth/periodontium followed by a discussion on successes to date, both in vitro and in vivo, toward regenerating a whole tooth and next steps required to regenerate a functional tooth.

Humans↗

PubMed2003

Amelogenin: a potential regulator of cementum-associated genes.

BACKGROUND: Studies suggest that enamel matrix proteins induce differentiation and mineralization of a variety of mesenchymal cells, including odontoblasts, osteoblasts, and cementoblasts. It has been postulated that this activity could be due to amelogenin-like proteins, known to be present in some mixtures of enamel matrix derivatives. Amelogenins have been reported to induce expression of a mineralized tissue-specific marker, bone sialoprotein (BSP), indicating that epithelial products can regulate the activity of mesenchyme-derived cells. METHODS: To explore the molecular mechanisms involved in BSP regulation, a clonal population of immortalized murine cementoblasts (OCCM-30) was exposed to full-length murine amelogenin protein (rp(H)M180), 0.1 microg/ml to 10.0 microg/ml, for 8 days in vitro. To further investigate the potential epithelial-mesenchymal interaction, an amelogenin knockout mouse model was used to examine expression of BSP and other markers, including Type I collagen, in tissue samples. RESULTS: The lowest dose of amelogenin slightly enhanced BSP expression, whereas at the highest dose, a dramatic decrease (three-fold) in BSP expression was observed. Parallel experiments showed a corresponding decrease in mineral nodule formation in vitro for cells treated with the higher dose of rp(H)M180. In situ hybridization and immunohistochemical analysis of sections from amelogenin null mice revealed a dramatic reduction in expression of BSP mRNA and protein in cementoblasts and surrounding osteoblasts in comparison to age-matched controls. In contrast, the expression of Type I collagen was not significantly different from controls. CONCLUSION: These data suggest that amelogenin may be a critical signaling molecule required for appropriate development of the periodontium.

Amelogenin↗

PubMed2003

Exploring the origins of cementoblasts and their trigger factors.

Future directions for designing periodontal regenerative therapies hinge on characterization of cells associated with periodontal tissues and on signals instrumental in regulating their behavior. Studies here focused on determining the responsiveness of putative cementoblast progenitor cells (follicle cells), periodontal ligament cells, and cementoblasts to specific factors. Cementoblasts (OCCM), periodontal ligament (SVPDL) cells, and follicle cells (SVF4) were isolated from mouse tissues and immortalized, where SV indicates the use of SV-40 for immortalization. Cultured cells were examined for response to parathyroid hormone-related protein (PTHrP), bone morphogenetic protein-2 (BMP-2), and enamel matrix derivative (EMD) using RT-PCR, Northern analysis, and in vitro and in vivo mineralization assays. Results showed that the three cell lines varied in their expression of bone sialoprotein (BSP) and osteocalcin (OCN), and in their capacity to promote mineralization. RT-PCR indicated that all cell lines had PTH/PTHrP-R1 and BMP receptors; however, the response of individual cell lines to PTHrP, BMP-2, and EMD was quite different. Such dissimilarities in responsiveness associated with cell type may need to be considered when designing regenerative therapies.

Animals↗