L-Carnitine Reduces Oxidative Stress and Promotes Cells Differentiation and Bone Matrix Proteins Expression in Human Osteoblast-Like Cells

Bone fragility and associated fracture risk are major problems in aging. Oxidative stress and mitochondrial dysfunction play a key role in the development of bone fragility. Mitochondrial dysfunction is closely associated with excessive production of reactive oxygen species (ROS). L-Carnitine (L-C), a fundamental cofactor in lipid metabolism, has an important antioxidant property. Several studies have shown how L-C enhances osteoblastic proliferation and activity. In the current study, we investigated the potential effects of L-C on mitochondrial activity, ROS production, and gene expression involved in osteoblastic differentiation using osteoblast-like cells (hOBs) derived from elderly patients. The effect of 5mM L-C treatment on mitochondrial activity and L-C antioxidant activity was studied by ROS production evaluation and cell-based antioxidant activity assay. The possible effects of L-C on hOBs differentiation were assessed by analyzing gene and protein expression by Real Time PCR and western blotting, respectively. L-C enhanced mitochondrial activity and improved antioxidant defense of hOBs. Furthermore, L-C increased the phosphorylation of Ca2+/calmodulin-dependent protein kinase II. Additionally, L-C induced the phosphorylation of ERK1/2 and AKT and the main kinases involved in osteoblastic differentiation and upregulated the expression of osteogenic related genes, RUNX2, osterix (OSX), bone sialoprotein (BSP), and osteopontin (OPN) as well as OPN protein synthesis, suggesting that L-C exerts a positive modulation of key osteogenic factors. In conclusion, L-C supplementation could represent a possible adjuvant in the treatment of bone fragility, counteracting oxidative phenomena and promoting bone quality maintenance

Betaine promotes cell differentiation of human osteoblasts in primary culture

BACKGROUND: Betaine (BET), a component of many foods, is an essential osmolyte and a source of methyl groups; it also shows an antioxidant activity. Moreover, BET stimulates muscle differentiation via insulin like growth factor I (IGF-I). The processes of myogenesis and osteogenesis involve common mechanisms with skeletal muscle cells and osteoblasts sharing the same precursor. Therefore, we have hypothesized that BET might be effective on osteoblast cell differentiation. METHODS: The effect of BET was tested in human osteoblasts (hObs) derived from trabecular bone samples obtained from waste material of orthopedic surgery. Cells were treated with 10 mM BET at 5, 15, 60 min and 3, 6 and 24 h. The possible effects of BET on hObs differentiation were evaluated by real time PCR, western blot and immunofluorescence analysis. Calcium imaging was used to monitor intracellular calcium changes. RESULTS: Real time PCR results showed that BET stimulated significantly the expression of RUNX2, osterix, bone sialoprotein and osteopontin. Western blot and immunofluorescence confirmed BET stimulation of osteopontin protein synthesis. BET stimulated ERK signaling, key pathway involved in osteoblastogenesis and calcium signaling. BET induced a rise of intracellular calcium by means of the calcium ions influx from the extracellular milieu through the L-type calcium channels and CaMKII signaling activation. A significant rise in IGF-I mRNA at 3 and 6 h and a significant increase of IGF-I protein at 6 and 24 h after BET stimulus was detected. Furthermore, BET was able to increase significantly both SOD2 gene expression and protein content. CONCLUSIONS: Our study showed that three signaling pathways, i.e. cytosolic calcium influx, ERK activation and IGF-I production, are enhanced by BET in human osteoblasts. These pathways could have synergistic effects on osteogenic gene expression and protein synthesis, thus potentially leading to enhanced bone formation. Taken together, these results suggest that BET could be a promising nutraceutical therapeutic agent in the strategy to counteract the concomitant and interacting impact of sarcopenia and osteoporosis, i.e. the major determinants of senile frailty and related mortality

Condylar morphology in growing patients related to vertical dimension.

Aim of the study was to evaluate the mandibular morphology, especially the condylar one, in growing patients, according to the different vertical patterns. The objective was to analyze which condylar dimensions significantly vary in low, normal and high angle divergency growing patients with the use of the orthopantomogram (OPG).From a database of randomly selected 514 patients, 96 subjects (48 males and 48 females) with skeletal Class I according to lateral cephalograms were selected and divided in three equal groups in relation to their vertical dimension (32 low FMA angle, 32 normal FMA angle and 32 high FMA angle). Each patient was examined with three OPGs at three different stages of dentition. OPGs were taken at the time of initial observation (T0 = first transitional phase of mixed dentition), after an average time of 12\ub11 months (T1=inter-transitional phase of mixed dentition) and after 36\ub13 months (T2=second transitional phase of mixed dentition). The radiological technician and the radiologic device were the same for each x-ray. On each OPG, condylar and mandibular ramus morphology of both sides was traced. Eleven linear and angular measurements were reported on each tracing. Data were analyzed by Wilcoxon's signed rank test and the Student's t-test.The study showed different condylar characteristics according to the vertical patterns. Differences were evident between males and females.The length of the mandibular ramus resulted longer in short-face patients respect to long-face subjects

Use of a flexible palatally positioned distalization appliance [Distalizzazione elastica graduabile]

Objectives: To describe the case of a 10-year-old boy with complete permanent dentition, Class II division I malocclusion and deep anterior bite. Materials and methods: The initial cephalometric tracing revealed a Class II hypodivergent pattern with reduction of the anterior facial height. The patient was treated with a flexible, palatally positioned orthodontic appliance for 7 months, after which a multibracket appliance (upper and lower arches) was used for approximately 18 months. Results and conclusions: The flexible distalizing device achieved distalization of upper molars, and the multibracket appliance allowed correction of the relationship between the two arches, producing a Class I occlusion of canines and molars and the correction of the overbite and overjet. \ua9 2011 Elsevier Srl. All rights reserved

Long-term periodontal response to orthodontic treatment of palatally impacted maxillary canines.

One of the most important aspects to take into consideration when evaluating the outcome of treatment of impacted maxillary canines is the final periodontal status. The aim of the present study was to evaluate the long-term periodontal response of palatally impacted maxillary canines aligned using a codified procedure and the 'Easy Cuspid' compared with contralateral spontaneously erupted teeth. The periodontal conditions of the adjacent teeth were also considered. From an initial sample of 124 patients, 33 patients (24 females and 9 males) were selected. All patients who had undergone surgical orthodontic treatment conducted in accordance with a standardized protocol were recalled for follow-up at an average of 4.6 years after the end of treatment. The average treatment time was 29 months and the mean eruption time of the previously impacted tooth was 3.1 months. The average probing depth values showed no significant clinical differences. Probing depths recorded at the vestibular surface of the lateral incisor (P < 0.05) and at the midpalatal/midlingual aspect of the first premolar were statistically significant in comparison with the control elements. Student's t-test was used to compare the test and control group values. Coefficient of reliability was set at P < 0.05. The use of a closed-flap surgical technique in association with a codified orthodontic traction system (Easy Cuspid) allowed alignment of palatally impacted canines without damage to the periodontium

Interdisciplinary treatment of Class III malocclusion: a case report.

The case report describes the multidisciplinary treatment of a 25-year-old male patient with a Class III malocclusion. Anterior and bilateral posterior crossbites were present. To correct the posterior crossbite a surgically assisted rapid maxillary expansion was performed. The significant three dimensional skeletal discrepancy was solved in a second phase with a surgical advancement of the maxilla. Functional and aesthetic occlusion in an improved facial profile was achieved with an interdisciplinary treatment that included orthodontic treatment, maxillofacial and periodontal surgery, and direct composite restorations