Stimulation of cell proliferation by calcium and a calcimimetic compound.

Some mesenchymal cells respond to stimulation by specific cations with increased cell proliferation. In the present study we have investigated whether the parathyroid/kidney/brain calcium-sensing receptor (PCaR) can mediate such mitogenic responses. We have expressed the recombinant rat PCaR in CCL39 hamster fibroblasts, which do not express a detectable endogenous cation sensor. The transfected cells responded to increased extracellular calcium concentrations ([Ca2+]e) with strong inositol phosphate (IP) formation, which was insensitive to pertussis toxin treatment of cells. We could not detect negative coupling of the receptor to adenylyl cyclase. The calcimimetic NPS R-568 left-shifted the concentration-response curve for [Ca2+]e-induced IP formation and increased the maximal response. In [3H]thymidine incorporation experiments, increasing [Ca2+]e from 1 to 4 mM was found to stimulate DNA synthesis weakly, but significantly. A strong potentiation of this response was observed in the presence of NPS R-568. [Ca2+]e and NPS R-568 also synergized to increase cell numbers in cultures maintained in defined medium. In contrast to our expectations, no significant stimulation of IP formation or cell proliferation could be observed after stimulation of cells with the reported PCaR agonist gadolinium (Gd3+) or with aluminum (Al3+), which stimulates osteoblast proliferation. Gd3+ actually inhibited IP formation stimulated by increased [Ca2+]e as well as by thrombin and AlF4-, indicating toxicity. However, submaximal receptor stimulation by Gd3+ was evident when intracellular calcium transients were measured in fluo-3-loaded cells. Our data show that PCaR can stimulate cell proliferation when expressed in an appropriate cellular context. However, it is unlikely that PCaR mediates the strong mitogenic effects elicited by the cations Gd3+ and Al3+ observed in osteoblasts.

Short - term effects of occlusal hypofunction following antagonist tooth extraction upon periodontal tissues in the rat.

This histological study was designed to observe the early effects of occlusal hypofunction on periodontal tissues. Eighteen Wistar rats were used. Hypofunction was induced by extracting the right maxillary molars. Histological observations were reported on the right lower jaws which were embedded in methyl-metacrylate, sectioned at 4 micrometer without decalcification and stained with toluidine blue. The periodontal ligament disorganization began after 2 days and continued until 16 days. The outstanding observation was a considerable increase in bone formation, which was responsible for ligament narrowing as no change in cementoblastic activity was observed. At the top of the interradicular septa, the osteoblastic proliferation began at 24 hours, and bone mineralization increased until 4 days creating osteophytic bone, and then decreased. On the modelling sides of the sockets, a great amount of osteoid tissue deposited by osteoblasts set around large vessels was present at 4 days, and mineralization extended between 4 and 8 days. On the remodelling sides, bone formation extended at 4 days and osteoclastic resorption fell of except along oblique roots sockets; then the remodelling sides returned to nearly normal aspect at 16 days. The biological significance and clinical implications of these findings are discussed.

Histologic study of the effects of occlusal hypofunction following antagonist tooth extraction in the rat.

A histologic study was done to observe the influence of occlusal hypofunction on periodontal tissues and the physiologic drift process, and to elucidate the origin of periodontal ligament narrowing. Twenty-four Wistar rats were used. Hypofunction was induced by extracting the right maxillary molars. Histologic observations were reported on the right lower jaws which were fixed, decalcified, sectioned and stained according to classical histologic methods. Two groups of five animals each were used for a complementary study study using sequential fluorescent labeling in order to evaluate the bone formation rate. After 15 days of hypofunction, the periodontal ligament was obviously narrowed and its structure was disorganized. Woven-bone formation was noted at the top of the interradicular septa, at the bottom of the sockets and along their modeling sides. At 30 days and at intervals up to 3 months, the periodontal ligament remained disorganized and narrowed. The newly-formed bone was engaged in a maturation process. Nevertheless, osteoporosis was also observed at the inferior part of the interradicular septa. Fluorescent labeling confirmed the histologic findings and showed that the induced bone formation is related to periodontal ligament narrowing and the supra-eruption process.

[Quantitative study of the effect of occlusal hypofunction on periodontal ligament with and alveolar osteoclastic resorption in rats]. / Etude quantitative des effets de l'hypofonction occlusale sur la largeur desmodontale et la résorption ostéoclastique alvéolaire chez le rat

An occlusal hypofunction has been produced by unilateral extraction of the maxillary molars in the rat and its effect has been studied on the antagonistic lower molars during a period of 15 days to 3 months. The quantitative analysis showed that the alveolar width decreased very significantly as early as the fifteen day. This fact was due to a decrease of the periodontal membrane width from the fifteenth day. This decrease was observed until 1 month on the alveolar surface undergoing apposition. The decrease of the alveolar width was also related to a drop of the periodontal membrane width as soon as fifteen days on the surface in resorption. The radicular width remained constant, confirming that it was the bone apposition and not the cementum apposition which caused the narrowing of the periodontal membrane. The quantitative study of the osteoclastic resorption showed that this later decreased but in a non significant on the alveolar surface undergoing remodeling.

[Quantitative study on the effects of occlusal overload on the remodelling of the alveolar process in the rat]. / Etude quantitative des effets d'une surcharge occlusale sur le remaniement de la paroi alvéolaire chez le rat

A quantitative study of alveolar bone resorption around the first lower rat molar has been conducted on horizontal sections. The number of osteoclasts/mm2 and the percentage of resorbing periodontal membrane surface of the socket rose through an increase in occlusal forces induced by an amalgam filling in slight occlusal overbite. The increase in resorption was significantly related to the duration of force application. The number of osteoclasts was more than tripled after 18 days. But this increase was observed in areas already previously submitted to osteoclastic resorption during bone remodeling associated with physiological tooth drift.