• Journal of Korean society of Dental Hygiene
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• v.23 no.4
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• pp.219-226
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• 2023

Objectives: This study aimed to investigate the effects of rhubarb extract on osteoclast differentiation in bone marrow-derived macrophages (BMMs). Osteoclasts are vital for bone resorption and remodeling. Osteoclast dysregulation can contribute to various bone-related disorders that directly affect oral health. Rhubarb, a medicinal plant with anti-inflammatory properties, has been shown to modulate bone metabolism. Methods: BMMs were isolated from the femurs and tibias of 5-week-old C57BL/6 mice and cultured in the presence of mouse macrophage colony-stimulating factor (M-CSF) for 3 days. Subsequently, BMMs were treated with M-CSF and receptor activator of nuclear factor-κB ligand (RANKL) to induce osteoclast differentiation. Results: Rhubarb extract effectively suppressed osteoclast differentiation in BMMs. Furthermore, rhubarb extract inhibited the mRNA expression of tartrate-resistant acid phosphatase (TRAP) and cathepsin K (CTSK), which are essential for osteoclastogenesis. Moreover, it inhibited the RANKL-induced expression of nuclear factor of activated T cell c1 (NFATc1), a crucial transcription factor in osteoclast differentiation. Conclusions: These results suggest that rhubarb extract promotes oral health by inhibiting osteoclastogenesis in BMMs. Thus, rhubarb extract shows promise as a therapeutic agent for bone-related disorders that directly affect oral health, particularly those associated with abnormal osteoclast activity. Further research and exploration of the underlying mechanisms are warranted to fully understand their potential clinical applications.

• Journal of Periodontal and Implant Science
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• v.53 no.2
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• pp.157-169
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• 2023

Purpose: The aim of this study was to evaluate the impact of polydeoxyribonucleotide (PDRN) on histologic outcomes when implant placement and lateral sinus floor elevation are performed simultaneously. Methods: Three bimaxillary premolars (P2, P3, and P4) were extracted from 4 beagle dogs 2 months before lateral sinus floor elevation. After lateral elevation of the sinus membrane, each sinus was allocated to either the test or control group. Sinuses underwent either 1) collagenated synthetic bone graft with PDRN following lateral sinus floor elevation (test group) or 2) collagenated synthetic bone graft without PDRN after lateral sinus floor elevation (control group). Eight weeks after the surgical procedure, all animals were euthanised for a histologic and histomorphometric assessment. Augmented height (AH), protruding height (PH), and bone-to-implant contact in pristine (BIC_p) and augmented (BIC_a) bone were measured. The composition of the augmented area, which was divided into 3 areas of interest located in coronal, middle and apical areas (AOI_C, AOI_M, and AOI_A), was calculated with 3 parameters: the area percentage of new bone (pNB), residual bone graft particle (pRBP), and fibrovascular connective tissue (pFVT). Results: AH, PH, BIC_p, BIC_a total, BIC_a coronal, and BIC_a middle values were not significantly different between sinuses in the control and test groups (all P>0.05). The BIC_a apical of sinuses in the test group (76.7%±9.3%) showed statistically higher values than those of sinuses in the control group (55.6%±22.1%) (P=0.038). pNB, pRBP, and pFVT showed statistically significant differences between the 2 groups in AOI_A (P=0.038, P=0.028, and P=0.007, respectively). pNB, pRBP, and pFVT in AOI_C and AOI_M were not significantly different between samples in the control and test groups (all P>0.05). Conclusions: The histologic findings revealed that lateral sinus floor elevation with PDRN might improve early new bone formation and enable higher bone-to-implant contact.

• Journal of Periodontal and Implant Science
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• v.54 no.2
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• pp.96-107
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• 2024

Purpose: Deproteinized bovine bone or synthetic hydroxyapatite are 2 prevalent bone grafting materials used in the clinical treatment of peri-implant bone defects. However, the differences in bone formation among these materials remain unclear. This study evaluated osteogenesis kinetics in peri-implant defects using 2 types of deproteinized bovine bone (Bio-Oss^® and Bio-Oss/Collagen^®) and 2 types of synthetic hydroxyapatite (Apaceram-AX^® and Refit^®). We considered factors including newly generated bone volume; bone, osteoid, and material occupancy; and bone-to-implant contact. Methods: A beagle model with a mandibular defect was created by extracting the bilateral mandibular third and fourth premolars. Simultaneously, an implant was inserted into the defect, and the space between the implant and the surrounding bone walls was filled with Bio-Oss, Bio-Oss/Collagen, Apaceram-AX, Refit, or autologous bone. Micro-computed tomography and histological analyses were conducted at 3 and 6 months postoperatively (Refit and autologous bone were not included at the 6-month time point due to their rapid absorption). Results: All materials demonstrated excellent biocompatibility and osteoconductivity. At 3 months, Bio-Oss and Apaceram-AX exhibited significantly greater volumes of formation than the other materials, with Bio-Oss having a marginally higher amount. However, this outcome was reversed at 6 months, with no significant difference between the 2 materials at either time point. Apaceram-AX displayed notably slower bioresorption and the largest quantity of residual material at both time points. In contrast, Refit had significantly greater bioresorption, with complete resorption and rapid maturation involving cortical bone formation at the crest at 3 months, Refit demonstrated the highest mineralized tissue and osteoid occupancy after 3 months, albeit without statistical significance. Conclusions: Overall, the materials demonstrated varying post-implantation behaviors in vivo. Thus, in a clinical setting, both the properties of these materials and the specific conditions of the defects needing reinforcement should be considered to identify the most suitable material.

• International Journal of Stem Cells
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• v.16 no.3
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• pp.342-355
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• 2023

Background and Objectives: Osteoblasts are derived from bone marrow mesenchymal stem cells (BMMSCs) and play important role in bone remodeling. While our previous studies have investigated the cell subtypes and heterogeneity in osteoblasts and BMMSCs separately, cell-to-cell communications between osteoblasts and BMMSCs in vivo in humans have not been characterized. The aim of this study was to investigate the cellular communication between human primary osteoblasts and bone marrow mesenchymal stem cells. Methods and Results: To investigate the cell-to-cell communications between osteoblasts and BMMSCs and identify new cell subtypes, we performed a systematic integration analysis with our single-cell RNA sequencing (scRNA-seq) transcriptomes data from BMMSCs and osteoblasts. We successfully identified a novel preosteoblasts subtype which highly expressed ATF3, CCL2, CXCL2 and IRF1. Biological functional annotations of the transcriptomes suggested that the novel preosteoblasts subtype may inhibit osteoblasts differentiation, maintain cells to a less differentiated status and recruit osteoclasts. Ligand-receptor interaction analysis showed strong interaction between mature osteoblasts and BMMSCs. Meanwhile, we found FZD1 was highly expressed in BMMSCs of osteogenic differentiation direction. WIF1 and SFRP4, which were highly expressed in mature osteoblasts were reported to inhibit osteogenic differentiation. We speculated that WIF1 and sFRP4 expressed in mature osteoblasts inhibited the binding of FZD1 to Wnt ligand in BMMSCs, thereby further inhibiting osteogenic differentiation of BMMSCs. Conclusions: Our study provided a more systematic and comprehensive understanding of the heterogeneity of osteogenic cells. At the single cell level, this study provided insights into the cell-to-cell communications between BMMSCs and osteoblasts and mature osteoblasts may mediate negative feedback regulation of osteogenesis process.

• Journal of Life Science
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• v.20 no.4
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• pp.607-613
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• 2010

Osteoporosis is a disease involving a decrease in bone mineral density and an increased risk of fractures. The MC3T3-E1 pre-osteoblastic cell line is a well-accepted model of osteogenesis in vitro. Pine needles have long been used as a traditional health-promoting medicinal food in Korea. In this study, MTT assay, the alkaline phosphatase (ALP) activity and collagen synthesis of osteoblast cells were investigated to determine the effects of pine needle extracts on cell proliferation and differentiation. Pine needle extracts were prepared using hexane, ethanol and water. The effects of the pine needle extracts were examined by comparing the results with those of commercial agents, such as proanthocyanidin. The MC3T3-E1 cells exposed to proanthocyanidin showed increased proliferation in a concentration-dependent manner. The cells exposed to the hexane extract showed a similar increase in proliferation to that observed with proanthocyanidin. The hexane extract showed the highest ALP activity. Moreover, a supplement of pine needle extracts induced collagen synthesis in MC3T3-E1 cells. The pine needle extract produced the highest level of collagen synthesis at concentrations of $10{\sim}50\;{\mu}g/ml$. These results indicate that pine needle extracts have an anabolic effect on bone by promoting osteoblastic differentiation, and may be used in the treatment of common metabolic bone diseases.

• The korean journal of orthodontics
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• v.32 no.6 s.95
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• pp.455-466
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• 2002

The objective of this study was to evaluate the changes that occurred over time in the distracted periodontal ligament space following the rapid retraction of a tooth by periodontal distraction after bone undermining surgery had been conducted in the dogs. The upper second premolars were extracted on the left and right side in 4 male beagle dogs. Immediately after extraction, the interseptal bone distal to the upper first premolar was thinned and undermined by grooving to decrease the bone resistance. Activating an individualized distraction appliance at the rate of 0.225mm twice a day, the upper first premolar was retracted rapidly toward the extraction socket. Periodontal distractions were performed for 5, 10, and 20 days, and 20-day-distraction cases were followed by maintenance periods of 0, 14, 28, and 56 days. After 20 days of rapid retraction, the average distal movement of the upper first premolar was 5.02mm, and the average mesial movement of the upper third premolars serving as an anchorage unit was 0.18 mm. On histological examination, the regeneration of bone occurred in a highly organized pattern. Distracted periodontal ligament space was filled with newly formed bone oriented in the direction of the distraction, and this was followed by extensive bone remodeling. This result was similar to those observed in other bones after distraction osteogenesis. In the periodontal ligament, the relationship between collagen fibers and cementum began to be restored 2 weeks after the distraction was completed, and showed almost normal features 8weeks after the completion of the periodontal distraction. However, on the alveolar side, the new bone formation was still in process and collagen fiber bundles and Sharpey's fibers were not present 8 weeks after the completion of the periodontal distraction. Reactions in the periodontal ligament of the anchorage tooth represented bone resorption on the compressed side and new bone deposition on the tension side as occurred in conventional orthodontic tooth movement. In conclusion, the results of this study showed that periodontal structures on the distracted side of the periodontal ligament were regenerated well histologically following rapid tooth movement.

• Journal of Acupuncture Research
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• v.26 no.2
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• pp.159-170
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• 2009

Backgrounds and Objectives: A fracture means a loss of continuity in the substance of bone. Bone differs from other musculoskeletal tissue due to its ability to repair and heal itself without leaving a scar. The cutter head has multinucleated osteoclast cells to resorb the dead bone. The tail, with its conical surface, is lined with osteoblast cells laying down new bone. The conjugation of fracture is a unique biological process regulated by a complex array of signaling molecules and proinflammatory cytokines. Pyritum, one of the important prescriptions in the oriental medicine, has been used for conjugation fracture. The purpose of this study is to evaluate the effects of administration of Pyritum on activation of osteoblast cells in human body & on tibia bone fracture in mice. Materials and Methods : Four weeks aged 30 female DBA mice were used for this study. They were divided three groups, normal group, control group(fracture elicitate mice: FE group) and experimental group(Pyritum administered mice group after fracture elicitation : PA group). Left tibia bones of mice in FE and PA groups were fractured by bone cutters. MG-63 cells in human body th Pyritum in the ratio of 1 mg/m${\ell}$, and the cells were further incubated for 24 hours. Activation of osteoblast was identified using osteopontin, FGF in vitro test. In vivo test, regeneration of fractured tibia through the morphological changes was observed, and also activation of inflammation through NF-${\kappa}$B p65, iNOS, COX-2, osteoblast through osteopontin, FGF and osteoblast's proliferation in each group was measured. Results and Conclusions : 1. In vitro test for activation of osteoblast cells in human body by Pyritum, osteopontin and FGF production were remarkably increased in Pyritum treated MG-63 cells. 2. In regeneration of fractured tibia by Pyritum, fractured area in external tibia morphology was decreased more in the PA group than that of the FE group. Osteogenesis in fractured area was increased more in the PA group than that of the FE group. Also, endochodrial ossification in central area of fracture and osteoid in lateral area of fracture were increased more in the PA group than those of the FE group. 3. In activation of inflammation by Pyritum administered, activation of NF-${\kappa}$B p65, increase of iNOS and COX-2 production were higher in the PA and the FE groups than those of the control group. Especially, the PA group showed higher activation and increase than those of the FE group. 4. In activation of osteoblast by Pyritum, increase of osteopontin, FGF and osteoblast's proliferation were higher in the PA and the FE groups than those of the control group. Especially, the PA group showed higher increase and proliferation than those of the FE group.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.4
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• pp.492-500
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• 2016

In this study, the effects of Colpomenia sinuosa (CS) extract on serum lipid level and bone formation in an ovariectomized animal model were investigated. Twenty four nine-week old female Sprague-Dawley rats were randomly assigned to four groups: sham-operated rats (SHAM), ovariectomized control rats (OVX-CON), and ovariectomized rats supplemented with CS extract at 50 mg/kg bw (OVX-CS50) or 200 mg/kg bw (OVX-CS200). Three OVX groups were surgically ovariectomized while the SHAM group was sham-operated. CS extract was orally administrated at 1 mL per day. Analysis of serum lipid contents found that the total cholesterol, triglyceride, and low density lipoprotein cholesterol levels in the OVX-CON group were higher than those in the SHAM group. Notably, upon administration of CS extract after ovariectomy, triglyceride levels tended to significantly decrease. In addition, platelet aggregation ability decreased in groups treated with CS extract compared to the OVX-CON group. Serum alkaline phosphatase activity as an indicator of bone formation was lower in the CS extract group compared to the OVX-CON group. Collagen contents in bone and cartilage were reduced by ovariectomy, whereas the CS extract-supplemented groups exhibited higher concentrations in bone. According to these results, CS extract improved serum lipid parameters and osteogenesis in ovariectomized rats.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.949-965
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• 1996

The main goal of periodontal therapy is to restore the lost periodontal tissue and establish the attachment appratus. Current acceptable therapeutic techniques are included : removal of diseased soft tissue, demineralization of exposed root surface, using the barrier membrane for preventing the downgrowth of gingival epithelial cell, insertion of graft materials as a scaffolding action, and biological mediators for promoting the cell activity. The latest concept one among them has been studied which based on the knowledge of cellular biology of destructed tissue. Platelet-derived growth factor(PDGF) is one of the polypeptide growth factor which have been reported as a biological mediator to regulate activities of wound healing progress including cell proliferation, migration, and metabolism. The purposes of this study is to evaluate the influences of the PDGF as biological mediator to periodontal ligament and bone marrow cell. Both right and left maxillary first molar were extracted from rat which had treated with 0.4% ${\beta}-Aminopropionitril$ for 5 days, and feeded until designed date to sacrifice under anesthesisa. Periodontal ligament were removed from the extracted socket of the rat, and cultured with Dulbecco's Modified Essential Medium(DMEM) contained with 10% Fetal Bovine Serum, 100U/ml penicillin, $100{\mu}g/ml$ streptomycin, $0.5{\mu}g/ml$ amphotericin-B. Bone marrow cell were culture from bone marrow suspension with which washed out from femur with same medium. The study was performed to evaluate the effect of PDGF to periodontal ligament and bone cell, cell proliferation rate, total protein synthesis, and alkaline phosphatase activity of rat periodontal ligament(PDL) cell and bone stromal(RBS) cell in vitro. The effects of growth factors on both cells were measured at 3, 5th day after cell culture with (control group) or without growth factors(experimental group). The results were as follows: 1. The tendency of cell proliferation under the influence of PDGF showed more rapid proliferation pattern than control at 3 and 5 days after inoculation. 2. The activity of Alkaline phosphatase revealed 14, 80% increased respectively at 3, 5 days culture than control group. Measurements of ALPase levels indicated that PDL cells had significantly higher activity when compared with that of co-culture groups and GF only(P<0.05). And, ALPase activity in 10 days was higher than that of 7 days(P<0.05). 3. The tendency of formation of the mineralized nodule were observed dose-depend pattern of PDL cells. There was statistically significant difference among group l(PDL 100%), 2(PDL 70%:GF 30%), and 3(PDL 50%:GF 50%)(P<0.01). But, there was no difference among group 3, 4(PDL 30%:GF 70%), and 5(GF 100%). 4. Also, the number of nodule was greater in co-culture of PDL 70% and GF 30% than in culture of PDL 70%(P<0.05). From the above results, it is assumed that the PDGF on PDL cells and RMB cell culture. GF stimulates the cell growth, which is not that of PDL cells but GF. And, the activity of ALPase depends on the ratio of PDL cells, and ALPase may relate to the initial phase of nodule formation. Also, it is thought that the calcified nodule formation principally depends on PDL cells, is inhibited by GF, and affected by cell density. In conclusion, platelet-derived growth factor can promote rapid osteogenesis during early stage of periodontal tissue regeneration.

• The Journal of Korean Academy of Prosthodontics
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• v.48 no.2
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• pp.128-134
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• 2010

Purpose: The aim of this study was to evaluate the changes in bone density and reduction of time consumed for osteogenesis by $PostPlant^{TM}$ Calcium and to find out efficacy of $PostPlant^{TM}$ Calcium by comparing the group prescribed with $PostPlant^{TM}$ Calcium with the group without $PostPlant^{TM}$ Calcium prescription. Material and methods: The experimental group of 18 patients with 25 dental implant placement and the control group of 7 patients with 9 dental implant placement were randomly selected from the patients who visited prosthetic department of Dankook University Dental Hospital since July, 2006 (IRB Number ; 20060710). The experimental group was instructed to take $PostPlant^{TM}$ Calcium for 6 months after the implant surgery while the control group was instructed not to. Both experimental and control group were assigned for measurement using $Osstell^{TM}$ Mentor and $Periotest^{(R)}$ and radiographic examination was performed using specifically manufactured Aluminum Step Wedge. The results were compared and analyzed. Results: 1. According to the $Osstell^{TM}$ Mentor measurement, both the experimental and control group showed increase in values as time elapses and the experimental group showed significantly higher rate of increase (P < .05). 2. According to the $Periotest^{(R)}$ measurement, both the experimental and control group showed decrease in values as time elapses. In addition, greater decrease can be seen in the experimental group but no statistical significance was found. 3. By examining the radiographic images, both the experimental and control group showed tendency of increase in bone density. In addition, greater increase can be seen in the experimental group but no statistical significance was found. Conclusion: Clinically, taking $PostPlant^{TM}$ Calcium medicine for a long period of time after implant placement is expected for a better prognosis.