Search

Elevated levels of prostaglandins such as PGE(2) in inflamed gingiva play a significant role in the tissue destruction caused by periodontitis, partly by targeting local fibroblasts. Only very few studies have shown that PGE(2) inhibits the proliferation of a gingival fibroblast (GF) cell line, and we expanded this research by using primary human GFs (hGFs) and looking into the mechanisms of the PGE(2) effect. GFs derived from healthy human gingiva were treated with PGE(2) and proliferation was assessed by measuring cell number and DNA synthesis and potential signaling pathways were investigated using selective activators or inhibitors. PGE(2) inhibited the proliferation of hGFs dose-dependently. The effect was mimicked by forskolin (adenylate cyclase stimulator) and augmented by IBMX (a cAMP-breakdown inhibitor), pointing to involvement of cAMP. Indeed, PGE(2) and forskolin induced cAMP generation in these cells. Using selective EP receptor agonists we found that the anti-proliferative effect of PGE(2) is mediated via the EP(2) receptor (which is coupled to adenylate cyclase activation). We also found that the effect of PGE(2) involved activation of Epac (exchange protein directly activated by cAMP), an intracellular cAMP sensor, and not PKA. While serum increased the amount of phospho-ERK in hGFs by approximately 300%, PGE(2) decreased it by approximately 50%. Finally, the PGE(2) effect does not require endogenous production of prostaglandins since it was not abrogated by two COX-inhibitors. In conclusion, in human gingival fibroblasts PGE(2) activates the EP(2)-cAMP-Epac pathway, reducing ERK phosphorylation and inhibiting proliferation. This effect could hamper periodontal healing and provide further insights into the pathogenesis of inflammatory periodontal disease., ((c) 2009 Wiley-Liss, Inc.)

One of the main theories which attempts to explain the phenomenon of tooth eruption suggests that periodontal ligament (PDL) fibroblasts move actively and pull the tooth with them out of its socket. To find further support for this theory, we determined the changes in the shape and orientation of PDL fibroblasts induced by a transition from impeded to unimpeded eruption. We measured nuclear area, elongation (length-to-width ratio), and orientation (angulation in relation to the eruption axis) of PDL fibroblasts in impeded (functionally loaded) and unimpeded (hypoloaded) rat incisors. The mean cross-sectional nuclear area did not differ between fibroblasts in the two groups. In contrast, unimpeded eruption resulted in a marked increase in the mean nuclear elongation (from about 2 to 2.56) and a significant increase in the mean nuclear orientation (from 25.6 to 14.0 degrees). Bivariate analysis suggested that these changes occurred in the same cells. Analysis of nuclear elongation and orientation at various distances from the cementum toward the alveolar bone revealed a profile of both parameters, such that cells located 20 to 80 microns away from the cemental surface were more elongated and more frequently oriented toward the eruption axis, while cells at 0 to 20 and 80 to 100 microns were more round/oval and had a greater angulation with the eruption axis. These findings, together with other observations of changes in cell number, number of microtubules, and migration velocity which occur on the shift to unimpeded eruption, support the theory of active movement of PDL fibroblasts as an important component of tooth eruption.

Titanium and hydroxyapatite are used for the fabrication of dental and orthopedic implants. The longevity of these implants depends on the amount and rate of bone formation that occurs around their surfaces. In the present study, the effects of titanium, hydroxyapatite, and polystyrene (control) on the proliferation of rat calvarial cells, and on their capacity to express alkaline phosphatase and respond to parathyroid hormone (PTH) stimulation, were studied. The nature of the substrate did not affect the DNA and protein contents of experimental and control cultures throughout the experimental period. Alkaline phosphatase expression and PTH response, as assessed by DNA synthesis and adenylate cyclase activity, were higher in cultures grown on hydroxyapatite and polystyrene than in those grown on titanium. These results indicate that hydroxyapatite was a more favorable substrate than titanium for the growth and differentiation of osteoblast-like cells in vitro.

Removal of the proliferating base of the rat incisor did not influence the rate of eruption which responded to changes in impediment to eruption in a fashion similar to that for control teeth. It is the peridontal ligament rather than the proliferating cells that is responsible for tooth eruption. The elements of the peridontal ligament apparently responsible for tooth movement are the mature fibroblasts.

Under conditions of high impediment, the rate of eruption of the rat incisor decreases considerably as does the rate of cell production of the inner enamel epithelium (IEE). The latter is acomplished by a decrease in the size of the proliferative compartment and an increase in the generation time. A linear relation exists between IEE cell production and tooth eruption, and cell production can be estimated from eruption measurements.

In the rat, the administration of a lathyrogenic agent reduced both impeded and unimpeded eruption rates of incisors. Unimpeded eruption rates were greater than impeded eruption rates. The general eruption pattern in the experimental rats was, however, similar to that in the control rats. Thus, eruption was possible even in rats with a lathyrogenically impaired periodontal ligament.

Crowning of all four rat incisors slows down their eruption rate, leading to a diminution of cell production by the inner enamel epithelium (IEE). The production rate by 100 progenitor cells is dominated as production rate %. The normal IEE in rats weighing 200 g produces daily 67 cells %. In the crowned incisor this rate drops to 15 cells % while during accelerated eruption rate and IEE cell production rate remains unchanged and an eruption of 6-4 mum reflects a production of 1 cell % by the IEE. A method which relates labelled cell displacement along the IEE with its cell production rate is described and its applicability to other cell renewal systems discussed.

A histologic and anatomic investigation of the symphyseal region in rabbits did not reveal a bony fusion between the two halves of the mandible; these two bones are united in the anterior part by a synchrondrosis, and a definite histologic suture with interdigitating bony rugosities and interposed connective tissue, in the posterior part. Functionally, the two parts are immobile and thus constitute one bone.

Thirty rats were divided into 3 equal groups. Following 9 days of induced unimpeded eruption, a single partial pulp resection was performed on the repeatedly-shortened lower left incisor of one group. A total of 3 resections, each repeated after 48 h, was performed on the animals in a second group. The lower left incisor was shortened but the pulp was not resected in the 3rd sham-operated control group. Eruption rates of all of the incisors were recorded daily. Partial resection of the pulp increased the unimpeded rate of the experimental incisors in the first group by 50 per cent at 24 h after operation and an increase occurred 3 times in the second group of rats (by 45, 36 and 25 per cent respectively). The rate returned to control levels 24 h later. No significant differences were observed between the eruption rates of the right maxillary and mandibular incisors of the animals in the 3 groups. The increased rate of eruption may be induced by local regulators from the traumatized pulp that are transmitted to components of the periodontal ligament which provide the force for eruption.

The mandibular condyles of 1,25(OH)2D3 or Vitamin D3 intoxicated rats were studied and compared with those of normal as well as pair-fed controls. Experimental animals were injected with either Vitamin D3 (2 mg/kg/day) or 1,25(OH)2D3 (400 ng/kg/day) for 19 days. Controls were given the solvent only, while pair-fed animals were restricted in their food intake for the same period of time, so that they exhibited a weight-curve similar to that of the experimental rats. The length of the mandibular ramus was measured in lateral radiographs of all mandibles. Demineralized coronal sections were obtained from all mandibular condyles and were stained with Mallory's connective tissue stain. The width of each zone within the condylar cartilage was measured. Experimental animals showed significant reduction in width of all layers within the condylar cartilage, with total lack of distinction between the maturation and hypertrophic zones. They also exhibited a significant retardation in growth of the mandible. Pair-fed animals had a normal width of the chondroprogenitor layer but significantly smaller maturation + hypertrophic zones (vs. controls). They also exhibited a significant retardation in mandibular growth but not to the same degree as did the intoxicated animals. Reduction in growth attributed to 1,25(OH)2D3 or Vitamin D3 intoxication is partly caused by undernutrition, which is a by-product of this condition. A further kinetic study is indicated to elucidate the mechanism of growth retardation and the differential effect on the various cartilage layers.