Regulation of osteoblast differentiation by Pasteurella multocida toxin (PMT): a role for Rho GTPase in bone formation.

The role of the Rho-Rho kinase signaling pathway on osteoblast differentiation was investigated using primary mouse calvarial cells. The bacterial toxin PMT inhibited, whereas Rho-ROK inhibitors stimulated, osteoblast differentiation and bone nodule formation. These effects correlated with altered BMP-2 and -4 expression. These data show the importance of Rho-ROK signaling in osteoblast differentiation and bone formation. INTRODUCTION: The signal transduction pathways controlling osteoblast differentiation are not well understood. In this study, we used Pasteurella multocida toxin (PMT), a unique bacterial toxin that activates the small GTPase Rho, and specific Rho inhibitors to investigate the role of Rho in osteoblast differentiation and bone formation in vitro. MATERIALS AND METHODS: Primary mouse calvarial osteoblast cultures were used to investigate the effects of recombinant PMT and Rho-Rho kinase (ROK) inhibitors on osteoblast differentiation and bone nodule formation. Osteoblast gene expression was analyzed using Northern blot and RT-PCR, and actin rearrangements were visualized after phalloidin staining and confocal microscopy. RESULTS: PMT stimulated the proliferation of primary mouse calvarial cells and markedly inhibited the differentiation of osteoblast precursors to bone nodules with a concomitant inhibition of osteoblastic marker gene expression. There was no apparent causal relationship between the stimulation of proliferation and inhibition of differentiation. PMT caused cytoskeletal rearrangements because of activation of Rho, and the inhibition of bone nodules was completely reversed by the Rho inhibitor C3 transferase and partly reversed by inhibitors of the Rho effector, ROK. Interestingly, Rho and ROK inhibitors alone potently stimulated osteoblast differentiation, gene expression, and bone nodule formation. Finally, PMT inhibited, whereas ROK inhibitors stimulated, bone morphogenetic protein (BMP)-2 and -4 mRNA expression, providing a possible mechanism for their effects on bone nodule formation. CONCLUSIONS: These results show that PMT inhibits osteoblast differentiation through a mechanism involving the Rho-ROK pathway and that this pathway is an important negative regulator of osteoblast differentiation. Conversely, ROK inhibitors stimulate osteoblast differentiation and may be potentially useful as anabolic agents for bone.     

Oral Fine Motor Control of Teeth Treated with Endodontic Microsurgery: A Single-Blinded Case-control Study

IntroductionPeriodontal mechanoreceptors (PMRs) are refined neural receptors present in abundance at the root apex and have a pivotal role in oral fine motor control. This case-control study aimed to evaluate the oral fine motor control of teeth treated with endodontic microsurgery (EMS) in comparison with the control teeth using a standardized behavioral biting task.MethodsFourteen eligible participants performed 5 trials of an oral fine motor control task that involved holding and splitting half of a peanut positioned on a force transducer with their EMS treated tooth and its contralateral control incisor tooth (28 teeth in total). The outcome variables were the mean food holding force, intra- and intertrial variability of the holding force, food splitting force, splitting duration, and the frequency of the stepwise splitting phase. The data were analyzed with parametric and nonparametric tests.ResultsThe results showed no statistically significant differences in the holding force, inter- and intratrial variability of the holding force, splitting force, or splitting duration between the teeth treated with EMS and the control (P > .05). However, there was a significantly higher frequency of stepwise ramp increase during the splitting phase with EMS treated teeth compared with the control (48% and 37%, respectively; P < .05).ConclusionsEMS treated teeth showed similar force regulation and oral fine motor control as the contralateral control. The findings of this study suggest that EMS treatment does not perturb the sensory information of PMRs and maintains the force regulation and oral fine motor control of the teeth.     

Bite or brain: Implication of sensorimotor regulation and neuroplasticity in oral rehabilitation procedures

Tooth loss, decreased mass and strength of the masticatory muscles leading to difficulty in chewing have been suggested as important determinants of eating and nutrition in the elderly. To compensate for the loss of teeth, in particular, a majority of the elderly rely on dental prosthesis for chewing. Chewing function is indeed an important aspect of oral health, and therefore, oral rehabilitation procedures should aim to restore or maintain adequate function. However, even if the possibilities to anatomically restore lost teeth and occlusion have never been better; conventional rehabilitation procedures may still fail to optimally restore oral functions. Perhaps this is due to the lack of focus on the importance of the brain in the rehabilitation procedures. Therefore, the aim of this narrative review was to discuss the importance of maintaining or restoring optimum chewing function in the superageing population and to summarise the emerging studies on oral motor task performance and measures of cortical neuroplasticity induced by systematic training paradigms in healthy participants. Further, brain imaging studies in patients undergoing or undergone oral rehabilitation procedures will be discussed. Overall, this information is believed to enhance the understanding and develop better rehabilitative strategies to exploit training‐induced cortical neuroplasticity in individuals affected by impaired oral motor coordination and function. Training or relearning of oral motor tasks could be important to optimise masticatory performance in dental prosthesis users and may represent a much‐needed paradigm shift in the approach to oral rehabilitation procedures.     

Platelet microvesicles are associated with the severity of coronary artery disease: comparison between peripheral and coronary circulation

Journal of Thrombosis and Thrombolysis - Microvesicles (MVs) have recently emerged as markers of thrombosis. Furthermore, there is an unexplained residual thrombotic risk is observed in patients...     

Inter-reader agreement of interpretation of radiological course of bile duct changes between serial follow-up magnetic resonance imaging/3D magnetic resonance cholangiopancreatography of patients with primary sclerosing cholangitis

Abstract

Objectives: Interpretation of MRI/MRCP in primary sclerosing cholangitis (PSC) at a single time point has low inter-reader agreement. Agreement of interpretation of the dynamic course of duct changes in follow-up MRI/MRCP is of clinical importance but remains unknown. Our aims are therefore to assess the inter-reader agreement of interpretation of the course of duct changes in PSC and investigate if elimination of 3?D MRCP affects inter-reader agreement.

Materials and Methods: We studied 40 consecutive PSC-patients who underwent two liver MRI/MRCPs at two time points. Two readers independently evaluated the course of duct changes between the two time points in two imaging sets, one with and one without 3?D MRCP. The intraclass correlation coefficient (ICC) was calculated for evaluation of inter-reader and intra-reader agreement between the two time points and two imaging sets accordingly.

Results: Inter-reader agreement of the interpretation of the course of duct changes between the two time points was poor (ICC up to 0.224). Elimination of 3?D MRCP neither improved inter-reader agreement which was again poor (ICC up to 0.26) nor did it change considerably the way readers interpret the course of ducts changes (ICC for intra-reader agreement between 0.809 and 0.978).

Conclusions: Inter-reader agreement of the interpretation of radiological course of duct changes is poor in serial follow-up MRI/MRCP of PSC-patients. Elimination of 3?D MRCP does not increase inter-reader agreement but maintains an excellent intra-reader agreement for the interpretation of the dynamic course of bile duct changes.

• Key points

• Inter-reader agreement of interpretation of radiological course of bile duct changes between serial follow-up MRI/MRCP examinations of patients with PSC is poor.

• Absence of 3D MRCP does not affect considerably the way readers interpret the radiological course of bile ducts changes.

• When MRCP is absent or of low quality, utilization of other sequences seems to be helpful as an alternative for bile duct evaluation.