Purpose: Placing dental implants in areas with low bone density or in conditions where bone healing is suppressed is challenging for clinicians. An experiment using a rodent model was performed with the aim of determining the efficacy of host modulation by increasing the systemic level of cholesterol sulfate (CS) using Irosustat in the context of the bone healing process around dental implants. Methods: In 16 ovariectomised female Sprague-Dawley rats, 2 implant fixtures were placed in the tibial bones (1 fixture on each side). At 1 week after surgery, the high-CS group (n=8) received Irosustat-mixed feed, while the control group (n=8) was fed conventionally. Block specimens were obtained at 5 weeks post-surgery for histologic analysis and the data were evaluated statistically (P<0.05). Results: Unlike the high-CS group, half of the specimens in the control group demonstrated severe bone resorption along with a periosteal reaction in the cortex. The mean percentages of bone-to-implant contact (21.5%) and bone density (28.1%) near the implant surface were significantly higher in the high-CS group than in the control group (P<0.05), as was the number of Haversian canals (by 5.3). Conclusions Host modulation by increasing the CS level may enhance the osseointegration of dental implants placed under conditions of impaired bone healing.

Pain management is an important part of dental practice, and dentists frequently prescribe analgesics to improve clinical outcomes. Dentists should be aware of the pharmacological characteristics of the analgesics commonly used in dentistry and should choose appropriate analgesics to treat and prevent pain associated with inflammation or surgery. In this article, we review the potential benefits and risks of the analgesics frequently used in dental practice and provide a stepwise approach for pain management.

Osteoporosis is a common disease characterized by bone mass reduction, leading to an increased risk of bone fracture, and it is caused by an imbalance of osteoblastic bone formation and osteoclastic bone resorption. Current osteoporosis drugs aim to reduce the risk of bone fracture, either by increasing osteoblastic bone formation or decreasing osteoclastic bone resorption. However, osteoblasts and osteoclasts are closely coupled, such that any reagent altering the differentiation or activity of one eventually affects the other. This tight coupling between osteoblasts and osteoclasts not only limits the therapeutic efficacy but also threatens the safety of osteoporosis drugs. This review will discuss the biological mechanisms of action of currently approved medications for osteoporosis treatment, focusing on the osteoblast–osteoclast coupling.
Bone Resorption ; Fractures, Bone ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteoporosis ; Population Characteristics

Inhibition of Rho-associated coiled coil-containing kinase (ROCK) has been reported to promote differentiation of neuronal cells. Here, we examined the effect of Y-27632, a ROCK inhibitor, on the outgrowth of neurites in PC12 cells. Y-27632 caused a rapid induction of neurite outgrowth in PC12 cells in a time-dependent manner. The neurite outgrowth, triggered by Y-27632, was accompanied by Rac1 activation, and was attenuated by Rac1 inhibitor NSC23766, in a concentration-dependent manner. Y-27632 also induced an increase in the production of reactive oxygen species (ROS). Pretreatment with N-acetylcysteine, an ROS scavenger, inhibited the ROS generation and neurite outgrowth in response to Y-27632. These results indicate that the activation of Rac1 and the generation of ROS contribute to the neurite outgrowth triggered by Y-27632 in PC12 cells.
Acetylcysteine ; Animals ; Neurites* ; Neurons ; PC12 Cells* ; Phosphotransferases ; Reactive Oxygen Species*

In the present study, we investigated the effect of staurosporine on the formation of cellular processes in human gingival fibroblasts and rat astrocytes. Staurosporine caused a rapid induction of process formation in human gingival fibroblasts and rat astrocytes in a concentration dependent manner. The process formation of human gingival fibroblasts and rat astrocytes was prevented by the pretreatment with N-acetylcysteine, suggesting that staurosporine-induced ROS production was responsible for the process formation. Colchicine, a microtubule depolymerizing agent, inhibited the staurosporine-induced process formation, whereas cytochalasin D, an actin filament breakdown agent, failed to suppress the formation of cellular processes. This result indicated that polymerization of microtubule, and not actin filament, was responsible for the formation of cellular processes induced by staurosporine. In support of this hypothesis, Western blot analysis was conducted using anti-tubulin antibody, and the results showed that the amount of polymerized microtubule was increased by the treatment with staurosporine while that of depolymerized beta-tubulin in soluble fraction was decreased. These results indicate that staurosporine induces ROS-mediated, microtubule-dependent formation of cellular processes in human gingival fibroblasts and rat astrocytes.
Acetylcysteine ; Actin Cytoskeleton ; Animals ; Astrocytes* ; Blotting, Western ; Colchicine ; Cytochalasin D ; Fibroblasts* ; Humans ; Microtubules ; Polymerization ; Polymers ; Rats* ; Staurosporine* ; Tubulin

Xylitol is a sugar alcohol with a variety of functions including bactericidal and anticariogenic effects. However, the cellular mechanisms underlying the role of xylitol in bone metabolism are not yet clarified. In our present study, we exploited the physiological role of xylitol on osteoclast differentiation in a co-culture system of osteoblastic and RAW 264.7 cells. Xylitol treatment of these co-cultures reduced the number of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cells induced by 10 nM 1alpha,25(OH)2D3 in a dose-dependent manner. A cell viability test revealed no marked cellular damage by up to 100 mM of xylitol. Exposure of osteoblastic cells to xylitol decreased RANKL, but not OPG, mRNA expression in the presence of 10(-8) M 1alpha,25(OH)2D3 in a dose-dependent manner. Furthermore, bone resorption activity, assessed on bone slices in the co-culture system, was found to be dramatically decreased with increasing xylitol concentrations. RANKL and OPG proteins were assayed by ELISA and the soluble RANKL (sRANKL) concentration was decreased with an increased xylitol concentration. In contrast, OPG was unaltered by any xylitol concentration in this assay. These results indicate that xylitol inhibits 1alpha,25(OH)2D3-induced osteoclastogenesis by reducing the sRANKL/OPG expression ratio in osteoblastic cells.
Acid Phosphatase ; Bone Resorption ; Cell Survival ; Coculture Techniques ; Enzyme-Linked Immunosorbent Assay ; Isoenzymes ; Osteoblasts ; Osteoclasts ; Proteins ; RNA, Messenger ; Vitamins ; Xylitol

The hyperosmotic stimulus is regarded as a mechanical factor for bone remodeling. However, whether the hyperosmotic stimulus affects 1alpha, 25-dihydroxyvitamin D3 (1alpha,25(OH)2D3)-induced osteoclastogenesis is not clear. In the present study, the effect of the hyperosmotic stimulus on 1alpha,25(OH)2D3-induced osteoclastogenesis was investigated in an osteoblast-preosteoclast co-culture system. Serial doses of sucrose were applied as a mechanical force. These hyperosmotic stimuli significantly evoked a reduced number of 1alpha,25(OH)2D3-induced tartrate-resistant acid phosphatase-positive multinucleated cells and 1alpha,25(OH)2D3-induced bone-resorbing pit area in a co-culture system. In osteoblastic cells, receptor activator of nuclear factor kappaB ligand (RANKL) and Runx2 expressions were down-regulated in response to 1alpha,25(OH)2D3. Knockdown of Runx2 inhibited 1alpha,25(OH)2D3-induced RANKL expression in osteoblastic cells. Finally, the hyperosmotic stimulus induced the overexpression of TonEBP in osteoblastic cells. These results suggest that hyperosmolarity leads to the down-regulation of 1alpha,25(OH)2D3-induced osteoclastogenesis, suppressing Runx2 and RANKL expression due to the TonEBP overexpression in osteoblastic cells.
Bone Remodeling ; Coculture Techniques ; Down-Regulation ; Osteoblasts ; RANK Ligand ; Sucrose

Differentiation of neuronal cells has been shown to accelerate stress-induced cell death, but the underlying mechanisms are not completely understood. Here, we find that early and sustained increase in cytosolic ([Ca2+]c) and mitochondrial Ca2+ levels ([Ca2+]m) is essential for the increased sensitivity to staurosporine-induced cell death following neuronal differentiation in PC12 cells. Consistently, pretreatment of differentiated PC12 cells with the intracellular Ca2+-chelator EGTA-AM diminished staurosporine-induced PARP cleavage and cell death. Furthermore, Ca2+ overload and enhanced vulnerability to staurosporine in differentiated cells were prevented by Bcl-XL overexpression. Our data reveal a new regulatory role for differentiation-dependent alteration of Ca2+ signaling in cell death in response to staurosporine.
Animals ; Calcium/*metabolism ; Caspase 3/metabolism ; Cell Differentiation/*physiology ; DNA Fragmentation ; Mitochondria/metabolism ; *Neurons/cytology/drug effects/physiology ; *PC12 Cells/cytology/drug effects/physiology ; Rats ; Staurosporine/*pharmacology ; bcl-X Protein/metabolism

BACKGROUND: The objects of this study is to compare the clinical aspects and characteristics of the sternal fracture between non-old aged and the old aged. METHODS: This study is based on 105 patients who were diagnosed as a sternal fracture at the emergency center of Chunchon Sacred Heart Hospital from January of 2001 to June of 2007. RESULTS: The overall clinical presentations of sternal fracture of the old aged are similar to that of non-old aged. There were some differences in the patterns of spinal fracture occurred with sternal fracture between non-old aged and the old aged. In non-old aged group, there were 7 patients(8.6%), who had the facture of spine along with sternal fracture, and there were 4 male and 3 females. In the old aged group, there were 4 male and 4 female patients out of 8 patients. There were 2 female patients who had both thoracic and lumbar spinal fractures in the old aged group. CONCLUSION: There were many cases of injury which were accompanied with the sternal fracture. When the two groups are compared, the spinal facture were more often in the old aged group. Especially, the fracture of lumbar spine occurred more frequent in the old aged group.
Emergencies ; Female ; Gangwon-do ; Heart ; Humans ; Male ; Spinal Fractures ; Spine ; Sternum

Synaptotagmin is a Ca2+ sensing protein, which triggers a fusion of synaptic vesicles in neuronal transmission. Little is known regarding the expression of Ca2+ - dependent synaptotagmin isoforms and their contribution to the release of secretory vesicles in mouse and rat parotid acinar cells. We investigated a type of Ca2+ - dependent synaptotagmin and Ca2+ signaling in both rat and mouse parotid acinar cells using RT-PCR, microfluorometry, and amylase assay. Mouse parotid acinar cells exhibited much more sensitive amylase release in response to muscarinic stimulation than did rat parotid acinar cells. However, transient [Ca2+]i increases and Ca2+ influx in response to muscarinic stimulation in both cells were identical, suggesting that the expression or activity of the Ca2+ sensing proteins is different. Seven Ca2+ - dependent synaptotagmins, from 1 to 7, were expressed in the mouse parotid acinar cells. However, in the rat parotid acinar cells, only synaptotagmins 1, 3, 4 and 7 were expressed. These results indicate that the expression of Ca2+ - dependent synaptotagmins may contribute to the release of secretory vesicles in parotid acinar cells.
Synaptotagmins/*metabolism ; Signal Transduction ; Rats ; Protein Isoforms/metabolism ; Parotid Gland/cytology/*metabolism ; Muscarinic Agonists/pharmacology ; Mice ; Exocytosis/drug effects/physiology ; Carbachol/pharmacology ; Calcium/metabolism/*physiology ; Animals ; Amylases/secretion