Engineered In vitro Models for Pathological Calcification: Routes Toward Mechanistic Understanding

Physiological calcification plays an essential part in the development of the skeleton and teeth; however, the occurrence of calcification in soft tissues such as the brain, heart, and kidneys associates with health impacts, creating a massive social and economic burden. The current paradigm for pathological calcification focuses on the biological factors responsible for bone-like mineralization, including osteoblast-like cells and proteins inducing nucleation and crystal growth. However, the exact mechanism responsible for calcification remains unknown. Toward this goal, this review dissects the current understanding of structure–function relationships and physico-chemical properties of pathologic calcification from a materials science point of view. We will discuss a range of potential mechanisms of pathological calcification, with the purpose of identifying universal mechanistic pathways that occur across multiple organs/tissues at multiple length scales. The possible effect of extracellular components in signaling and templating mineralization, as well as the role of intrinsically disordered proteins in calcification, is reviewed. The state-of-the-art in vitro models and strategies that can recreate the highly dynamic environment of calcification are identified

Cell division, synthetic capacity and apoptosis in periodontal lesions analysed by in situ hybridisation and immunohistochemistry

In this study, we investigated the synthetic and proliferative activity of infiltrating mononuclear cells in sections of granulation tissue from periodontitis lesions in both adult periodontitis (AP) and early onset periodontitis (EOP) patients. We also investigated the role of apoptosis in the remodelling of the inflamed tissue. We utilised a Ki-67 antigen specific antibody and a histone messenger RNA (mRNA) probe to detect cells undergoing cell division in the sections. Oligonucleotide probes for 28S ribosomal RNA and for the detection of poly A mRNA were utilised to detect cells with synthetic capacity. Apoptosis was determined using terminal transferase labelling of fragmented DNA with Biotin labelled dUTP. Biopsies of granulation tissue were obtained from 9 AP patients, from 10 EOP patients and for comparative purposes, biopsies of gingival tissue from 4 patients with AP. There were no differences regarding the relative proportions of cells with synthetic capacity or in the numbers of dividing cells in the periodontitis tissue sections. However, we observed an increase in the number of dividing cells in the AP granulation tissues compared to the AP gingival sections and that these cells were predominantly fibroblast like in appearance. Apoptotic cells consisted mainly of connective tissue cells; mainly fibroblasts with few if any leukocytes being apoptotic other than polymorphonuclear leukocytes. Only a few cyto-phagocytic macrophages were ever observed in the gingival and granulation tissues. We conclude that the turnover of infiltrating leukocytes in inflamed periodontal tissue is low, that they probably arrive at this site by recruitment from distant lymph nodes, and that neither cell division nor programmed cell death significantly alter the numbers of inflammatory cells. On the other hand, fibroblast apoptosis and cell division occur within the periodontium as these are typical processes in the normal turnover and remodelling of these tissues

Periodontal changes following molar intrusion with miniscrews

BACKGROUND: With the introduction of skeletal anchorage system, recently it is possible to successfully intrude molar teeth. On the other hand, there have been concerns about periodontal changes associated with intrusion and there are few studies on this topic, especially for posterior teeth. MATERIALS AND METHODS: Ten female patients were enrolled in this study. Maxillary molar intrusion was achieved by inserting two miniscrews and a 17 × 25 titanium molybdenum alloy spring. Crestal height changes were evaluated at three intervals including: Baseline (T0), end of active treatment (T1) and 6 months after retention (T2). Other variables including probing depth, gingival recession, attachment level and bleeding on probing were evaluated by clinical measurements in the three above mentioned intervals. One-sample Kolmogrov-Smirnov test ascertained the normality of the data. For all patients, the changes in tooth position and crestal height were evaluated using one-sample t-test. (P < 0.05). RESULTS: Supra-erupted molars were successfully intruded a mean of 2.1 ± 0.9 mm during active treatment (T0-T1). A mean bone resorption of 0.9 ± 0.9 mm in mesial crest and 1 ± 0.8 mm in distal crest had occurred in total treatment (T0-T2). A mean of 0.6 ± 1.4 mm bone was deposited on mesial crest during the retention period (T1-T2) following tooth relapse. On average, 0.8 ± 0.4 mm attachment gain was obtained. Gingival margin coronalized a mean of 0.8 ± 0.6 mm throughout the entire treatment. Probing depth showed no significant change during treatment. CONCLUSION: Within the limitations of this study, these results suggest that not only periodontal status was not negatively affected by intrusion, but also there were signs of periodontal improvement including attachment gain and shortening of clinical crown height