ABSTRACT— Twenty male adult rats weighing 200 g were injected with tritiated thymidine (3HTdR). The animals were then killed in groups of five, at the following times: 1 h, 1, 3 and 5 weeks. Autoradiograms of sections through the liver were prepared. The distances between labelled cells and the portal space rim were measured. One hour after labelling most labelled cells were confined to a region extending from the portal space rim up to a distance of 700 μm, which roughly corresponds to Rappaport's hepatic acinus zones‐1 and ‐2. Throughout the experiment lasting 5 weeks labelled cells entered zone‐3 and advanced toward the terminal hepatic vein. Hepatocytes travelled at a daily velocity of 1.44 μm, covering daily 0.324% of the acinus diameter. During the experiment acinus size did not change appreciably. The estimated mean hepatocyte cell cycle time was 37 days and its life expectation, 201 days. These experiments show that the liver is essentially a slowly renewing cell population. Hepatocytes nascent at the portal space gradually stream toward the terminal hepatic vein where they are probably eliminated by apoptosis. Their journey lasts 201 days. Since hepatocytes are glued together with tight junctions, all have to advance toward their terminal hepatic veins en masse. During their voyage, they traverse the three acinus zones, and since in each they produce different enzymes, each zone represents a differentiation state of the advancing cell. It is suggested further that the streaming hepatocyte carries with it its nerve supply and is accompanied by sinusoidal endothelium and Kupffer cells.

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.

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.

We examined the effect of function on tooth and periodontal ligament (PDL) morphology in 40 lower incisors of adult female rats. Ten teeth were exposed to occlusal hyperfunction for three months, ten to hypofunction for three weeks, ten to hypofunction for three months, while ten teeth in normal occlusion served as control. Transverse ground sections were cut at various levels perpendicular to the tooth long axis, and their distances from the apex were calculated. The outlines of the tissues were traced and fed into a computer. We plotted the measurements according to their location and fitted them by second-order polynomials. We calculated tissue volume for the proximal 18 mm of bone-embedded tooth. Hyperfunction affected tooth shape, in that it became more rounded. The volumes of the dental tissues remained unchanged, while width and volume of the cementum-bordering PDL increased. Hypofunction did not alter tooth shape, but influenced its size: After three weeks, tooth circumference decreased, and after three months, it expanded. Dentin width was reduced, with concomitant increase of pulp size. The amount of enamel diminished initially, but after three months returned to normal values. The PDL bordering enamel expanded proportionally to the duration of hypofunction. The changes in socket size reflected the total dimensional variations in the tooth and its PDL. The results demonstrate that the shape and size of growing teeth and their periodontium are influenced by functional occlusal forces.

Removal of occlusal contact in the absence of attrition liberates the growth potential of the rat incisor, which is expressed in a doubled rate of axial growth and eruption. The differentiation times, the life spans and the rates of apposition of dental hard tissue-forming cells, however, are independent of the rates of growth and eruption.