Dental implications of pharmacological management of the Alzheimer's patient.
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Biomedical subjects
Publications and source records attributed to M J Somerman.
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Dentin matrix was assayed for its potential to elicit chondrogenesis of mesenchymal cells in vitro. The substratum was prepared by demineralization of human tooth root dentin, while embryonic thigh muscle was used as a source of mesenchymal cells. Formation of chondrocytes from mesenchymal cells occurred in the presence of dentin matrix, and in the same sequence as previously shown with substrata of demineralized bone.
A primary objective in the treatment of periodontal diseases is attachment of fibrous tissue to root surfaces. An in vitro method was used to evaluate agents for their potential in enhancing this attachment process. Guanidine EDTA protein extracts of alveolar bone, cementum, and dentin in culture media were added to petri dishes and incubated at 37 degrees C for 1 hour. Human gingival fibroblasts were added to the dishes and incubated for an additional 90 minutes. Following incubation, cells attaching to the dish were quantified electronically, using a Coulter Counter. Extracts of alveolar bone and cementum enhanced cell attachment while dentin extract had no effect. These results indicate that both cementum and bone contain attachment proteins which could prove beneficial for attachment of fibrous tissue to root surfaces.
Effects of phenytoin (DPH) on parathyroid hormone (PTH)- and 1,25-dihydroxyvitamin D3(1,25DHCC)-mediated bone resorption in bone organ culture were evaluated: it markedly inhibited the actions of both. However, PTH tended to overcome the initial effects of DPH, whereas bone resorption due to 1,25DHCC remained depressed as if DPH treatment had continued. Thus DPH-induced bone abnormalities may involve a greater direct effect on 1,25DHCC regulation of bone homeostasis than on PTH.
Cementum is a specialized mineralized tissue providing for the attachment of periodontal fibers to the root surface of a tooth. In periodontal disease this connective tissue attachment to the cemental surface is lost. The ability of bacteria to adhere to the root surface, an initial event in the disease process, may be influenced by the organic matrix of cementum. Therefore, an in vitro assay of cell attachment was modified to study bacterial adherence to protein extracts of cementum. Petri dishes coated with the extracts were pre-incubated in culture media and then bacteria were added. Using this assay, Capnocytophaga-like species, a gram negative bacterium implicated in periodontal disease, attached preferentially to dishes coated with cemental extracts when compared with Type I collagen or uncoated dishes. This assay system should prove beneficial for studying the attachment of various microorganisms to protein extracts of both normal and diseased cementum, as well as providing insight into the unique attachment properties of cementum.
Weanling rats were given a vitamin D-deficient diet containing 1.4% calcium and 1.0% phosphorus. After 4 weeks these deficient animals were injected for 7 days with selected doses of one of the following vitamin D metabolites: 25(OH)D3, 1,25(OH)2D3, 24,25(OH)2D3, 25,26(OH)2D3 or the ethanol vehicle. A vitamin D-replete group was placed on the same diet but injected with 50 IU of vitamin D3 once a week for the entire 5-week period. By the use of a modified Ussing chamber [1], the measurements of calcium fluxes into and from the rat calvaria were possible. These data enabled the apparent mineral solubilities to be derived. After 5 weeks on this diet the vitamin D-deficient rats had low levels of serum calcium (1.41 mM) and decreased mineral solubility when compared to the vitamin D-replete group. The apparent solubility of the bone mineral increased toward the vitamin D-replete level in calvaria from vitamin D metabolite-treated rats. However, these changes did not directly reflect the alterations in the level of serum calcium. At any given dose level, 1,25(OH)2D3 was the most effective metabolite in increasing serum calcium. In fact, the high dose (250 pmoles/day) was hypercalcemic. Next in effectiveness was 25(OH)D3. These two metabolites were equally effective in increasing mineral solubility. At a 10 times higher dose, the 24,25(OH)2D3 metabolite was able to normalize serum calcium and improve but not normalize mineral solubility. At the high dose (260 pmoles/day), the 25,26(OH)2D3 metabolite caused no effect on mineral solubility and minimal increases in serum calcium.
For the first time, mononuclear cell-mediated ingestion of osteoid in cultures of long bones of fetal rats is described and characterized. The mononuclear cells, located at sites of osteoid deposition, ingest collagen fibrils and clumps of mineral crystals which are segregated within cytoplasmic vacuoles or multivesicular bodies. The ingestion of osteoid continues in cultures treated with agents that normally inhibit osteoclastic bone resorption. Morphologically, the osteoid-containing cells are characterized by a moderate number of mitochondria and short-stranded rough endoplasmic reticulum, a modest Golgi apparatus and variable numbers of vesicles, vacuoles, and multivesicular bodies. The morphologic appearance of the mononuclear cell is consistent with that of a macrophage.
Studies employing the matrix-induced endochondral bone formation system have outlined the processes involved in bone induction. An initial event is increased migration of mesenchymal cells to the implant site prior to endochondral calcification. This suggests that chemotactic factors in the bone matrix may be involved in the osteogenic process. Extracts of human fetal bone, obtained by sequential demineralization, stimulated the migration of osteoblast-like cells in a dose-dependent fashion, as assayed in the Boyden chamber. In contrast, comparable extracts of normal adult bone (40-year-old male) did not stimulate osteoblast migration. Monocytes, potential osteoclast precursors, did not migrate in response to either of these extracts. These studies suggest that significant differences exist in protein composition and/or distribution between fetal and adult human bones. These differences may well influence the remodeling potential of these bones.
Adhesion molecules are considered to have an active role in controlling cell differentiation, although the mechanisms involved have yet to be determined. The developing tooth provides an excellent model to use for determining the factors/processes regulating cell differentiation. The studies presented here focused specifically on the timed and spatial expression of a bone-associated adhesion molecule, bone sialoprotein, during tooth root development. Mandibular tissues in the first molar region of CD-1 mice, at sequential stages of development, were analysed by in situ hybridization. The results demonstrate distinct expression of bone sialoprotein in surrounding bone at early stages of tooth development. At stages of active cementogenesis, bone sialoprotein transcripts were specific to cells lining the root surface, with limited expression in the surrounding connective tissue (periodontal ligament) region. The strong expression of bone sialoprotein, a mineral-specific protein having the capacity to act as a nucleator of hydroxyapatite in vitro, by cells lining the root surface at early stages of cementogenesis suggests that this molecule is operative in the cell/matrix events that accompany cementum formation.