In response to PTH treatment, the results showed a similar patter

In response to PTH treatment, the results showed a similar pattern

of variation for BGN and COL1 mRNA expression. Both BGN and COL1, after 24-h/cycle and continuous PTH treatment, showed a higher BGN and COL1 expression than the Control group, and this data are not correlated with mineral deposition. The MMPs are gelatinases with collagen-degrading ability, and presumably contribute to organic matrix reorganization during the dentine mineralization.32 In addition, some of these enzymes are incorporated into dentine, since at least gelatinase A (MMP-2) and enamelysin together with a yet unidentified latent collagenolytic enzyme have been found in dentine.32 Although no changes were verified in MMP-2 mRNA levels, we found, by zymographic assay, that PTH modulates the MMP-2 secretion in MDPC-23 Selleck Anti-infection Compound Library cells by time-dependent manner. The 1-h/cycle treatment with PTH up-regulated the secreted levels of the intermediate (∼68-kDa) and active (∼62-kDa) forms of the MMP-2 in relation to Control group, whereas, the continuous PTH stimulation decreased the MMP-2 active-form secretion. PTH can induce MMP-2 secretion in growth plate chondrocyte cultures, and its induction is involved in the programmed

extracellular matrix degradation Obeticholic Acid molecular weight during endochondral bone formation.33 The decrease of calcium deposition by treatment of PTH during 1-h/cycle correlates with an increase of MMP-2 secretion. We hypothesized that MMP-2, in this case, could accelerate ECM degradation (COL1 and BGN), and, therefore, disturb the posterior calcium deposition. In contrast with our previous study which demonstrated that intermittent PTH administration caused an anabolic effect during mice dentine formation,15 the present study shows that the intermittent PTH administration (1 and 24-h/cycle) modulates odontoblast-like cells differentiation, decreasing the calcium

Clostridium perfringens alpha toxin deposition. The suppression of the calcium deposition has also been observed after in vitro PTH exposure to primary calvarial osteoblasts, calvarial explants, osteoblast-like cell lines and cementoblasts. 34 and 35 The causes of the different response of the odontoblast-like cells to continuous or intermittent treatment is unknown, but it was demonstrated that PTH has diverse effects on osteoblast differentiation depending on the exposure time in vitro mediated through different signal transduction systems. 17 Similarly to our results to odontoblast-like cells, Ishizuya et al. 17 found that when osteoblasts are exposed intermittently to PTH only for the first hour of each 48-h incubation cycle, ALP activity, expression of ALP and osteocalcin mRNAs, and the formation of bone nodules are inhibited compared to cells free from PTH treatment, and that cAMP/PKA is the major signal transduction system involved in the inhibitory effect of 1-h intermittent exposure to PTH in osteoblasts.

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