• The Korea Journal of Herbology
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• v.36 no.5
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• pp.81-91
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• 2021

Objectives : Osteoporosis is a systemic skeletal disease that decreases bone density and increases the risk of fractures. Bisphosphonates and SERMs are mainly used to treat osteoporosis, but, long-term use increases the risk of side effects such as jaw bone necrosis and breast cancer. Therefore, it is necessary to develop a therapeutic agent for a natural product with few side effects. Water extract of Lonicerae Japonicae Flos (wLF) was mainly found to have anti-cancer and anti-inflammatory effects. However, the effect of wLF on osteoporosis has not been elucidated. Therefore, this experiment investigated the effect of wLF on osteoclasts, osteoblasts and osteoporosis models. Methods : In order to study the effect of wLF on osteoporosis, the OVX-induced rat model was used for in vivo study. After 8 weeks, we measured body weight, uterine weight, liver weight, femur weight, bone density, trabecular area and tibia ash weight. To determine the effect of wLF on osteoclast differentiation, we measured the number of TRAP-positive cells and TRAP activity. To examine the effect of wLF on the expression of osteoblast-related genes, we measured the mRNA expression of alkaline phosphatase (ALP, Alpl) and osteocalcin (OCN, Bglap2). Results : In vivo experiment, wLF inhibited the reduction of femur weight, trabecular area, bone density and tibia ash weight. In vitro experiment, wLF had no significant effect on osteoclast differentiation. However, wLF increased the mRNA expression of Alpl and Bglap2 in MC3T3-E1 cell. Conclusions : This result suggested that wLF may be used for the treatment and prevention of postmenopausal osteoporosis.

• Journal of Food Hygiene and Safety
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• v.37 no.5
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• pp.364-371
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• 2022

The bones of the human body support the structures of the body and provide protection for a person's internal organs. Bone metabolic diseases are on the rise due to a significant increase in life expectancy over a short period of time. Therefore, we investigated the osteoblast differentiation promoting and osteoclastogenesis inhibitory activities of fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf). We evaluated the alkaline phosphatase (ALP) activity of MC3T3-E1 mouse calvarial-derived osteoblasts. We also evaluated expression of ALP, osteocalcin (OCN), and runt-related transcription factor 2 (Runx2), which regulate osteoblast differentiation. To assess effects on osteoclast formation, tartrate-resistant acid phosphatase (TRAP) activity in RAW264.7 cells was analyzed. ALP activity increased by 121-136% and 140-156%, respectively in the presence of HR1901-BS and HR1901-BSaf. Expression of osteoblast differentiation factor also increased significantly. We also confirmed that HR1901-BS and HR1901-BSaf decreased TRAP activity in osteoclasts by 35-47% and 23-39%, respectively. Our results showed that fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf) increase bone mineralization and osteoblast differentiation activity in MC3T3-E1 cells, and inhibit bone resorption activity in RAW264.7 cells. In conclusion, fermented Benincasa hispida cong. (HR1901-BS, HR1901-BSaf) can be used as an effective natural resource for preventing and treating bone-related diseases.

• IMMUNE NETWORK
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• v.21 no.6
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• pp.43.1-43.14
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• 2021

Group 3 innate lymphoid cells (ILC3), which express IL-22 and IL-17A, has been introduced as one of pathologic cells in axial spondyloarthritis (axSpA). Dyslipidaemia should be managed in axSpA patients to reduce cardiovascular disease, and dyslipidaemia promotes inflammation. This study aimed to reveal the role of circulating ILC3 in axSpA and the impact of dyslipidaemia on axSpA pathogenesis. AxSpA patients with or without dyslipidaemia and healthy control were recruited. Peripheral blood samples were collected, and flow cytometry analysis of circulating ILC3 and CD4⁺ T cells was performed. The correlation between Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-reactive protein (CRP) and circulating immune cells was evaluated. The effect of oxidized low-density lipoprotein cholesterol (oxLDL-C) on immune cell differentiation was confirmed. AxSpA human monocytes were cultured with with oxLDL-C, IL-22, or oxLDL-C plus IL-22 to evaluate osteoclastogenesis using tartrate-resistant acid phosphatase (TRAP) staining and real-time quantitative PCR of osteoclast-related gene expression. Total of 34 axSpA patients (13 with dyslipidaemia and 21 without) were included in the analysis. Circulating IL-22⁺ ILC3 and Th17 were significantly elevated in axSpA patients with dyslipidaemia (p=0.001 and p=0.034, respectively), and circulating IL-22⁺ ILC3 significantly correlated with ASDAS-CRP (Rho=0.4198 and p=0.0367). Stimulation with oxLDL-C significantly increased IL-22⁺ ILC3, NKp44^- ILC3, and Th17 cells, and these were reversed by CD36 blocking agent. IL-22 and oxLDL-C increased TRAP⁺ cells and osteoclast-related gene expression. This study suggested potential role of circulating IL-22⁺ ILC3 as biomarker in axSpA. Furthermore, dyslipidaemia augmented IL-22⁺ ILC3 differentiation, and oxLDL-C and IL-22 markedly increased osteoclastogenesis of axSpA.

• The korean journal of orthodontics
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• v.34 no.1 s.102
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• pp.71-81
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• 2004

In this study, we attempt to investigate the mechanisms by which PDL cells regulate osteoclast formation and also tc know whether PDL retained their characteristic phenotype during tooth eruption and interdental separation. Rats were prepared at developmental days 21 (pre-root formation), 27(toot development), 34(advanced root formation/eruption) and at later times(adult rats). To induce severe resorption state of alveolar bone and tooth root, interdental separation with brass wire was performed between the lower first and second molars for 2 weeks in adult rats. Rat mandibles were demineralized and embedded in paraffin, and horizontal and frontal section were prepared for immuno-histochemical analysis using PDL-specific protein 22 (PDLs22), receptor activator of NFKB ligand (RANKL) and osteoprotegerin (OPG) antibodies. 1. Root formation and eruption stage of tooth development. 1) PDLs22 immunolocalization was observed in tooth follicle/PDL cells and osteoblasts throught out the root formation and eruption stages of tooth development. 2) RANKL expression became stronger at eruption stage than root formation stage of tooth development. 3) Strong expression of OPG was detected in follice/PDL cells of toot formation stage but it was decreased with tooth eruption. 2. Interdental separation between lower first and second molar 1) Comparared to normal animal, multinucleated osteoclasts and odontoclasts were markedly induced in the alveolar bone and tooth root with PDL remodeling in hematoxylin-eosin section. 2) PDLs22 expression was decreased with interdental separation. 3) RANKL expression was Increased with interdental separation in PDL fibroblasts, osteoblasts, odontoclasts and it lacunae, resorting dentin, cementum and bone matrix. 4) OPG expression was slightly decreased in the PDL cells adjacent to the alveolar bone and root surface with interdental separation. These results suggested that during tooth eruption and tooth movement, RANKL and OPG in the periodontal tissues are important determinants regulating balanced alveolar bone and tooth root resorption. And it is also suggested that PDL cells retained their characteristic phenotype during tooth eruption and interdental separation except for the short period of PDL remodeling.

• The korean journal of orthodontics
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• v.28 no.1 s.66
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• pp.85-97
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• 1998

The purpose of this study was to observe the effects of sodium fluoride on the bony repair and regeneration processes after the rapid palatal expansion in the growing dogs. Eighteen dogs were divided into experimental and control groups. They were in the late mixed dentition. The rapid Palatal expansion was undertaken in all the animals($180^{\circ}$ turn/day) for ten days. The animals were sacrificed on 0, 15 and 45 days after the finish of expansion. One mg NaF/kg of body weight/day were given orally to the experimental group. Blood samples were drawn before and after expansion and the se겨m calcium, phosphate and alkaline phosphatase level were measured. The undecalcified bone section of midpalatal suture area was made, and observed under the light microscopy The results were as follows ; 1. The day after expansion, the infiltration of inflammatory cells were prominent and the new bone formation started at the edges of the two palatal plates bodering the midpalatal suture in both groups. Especially, the newly formed osteoid were very extensive and the osteoblasts lining the osteoid were very active in the experimental group. 2. At fifteen days after expansion, the active osteoblasts lining the osteold at the surface of trabecular bony spicules and active new bone formation were observed in the both groups. However, the cellular activity and new bone formation were more prominent In the experimental group. 3. At forty five days after expansion, the continuous osteoid and new bone formation and active osteoblasts were observed in the experimental group. But these phenomena were not observed in the control group. In the control group, the numerous osteoclasts were adjacent midpalatal suture and the bony remodeling process was begun. The serum alkaline phosphatase level was maintained highly in the experimental group, but decreased in the control. According to the above results, the author reached the conclusion that sodium fluoride has the stimulation effects on the osteoid production of the osteoblasts during the healing process after the rapid Palatal expansion more continuously.

• The korean journal of orthodontics
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• v.31 no.4 s.87
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• pp.447-458
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• 2001

The purpose of this study was to evaluate 1) in vivo, the expression of chondroitin 4-sulfate (CH-4S), a structural element of glycosaminoglycans(GAGs), in periodontal tissue during the experimental movement of rat incisors, by labelled streptavidine biotin immunohistochemical staining for CH-4S, 2) In vitro, the expression of CH-4S in cultured human periodontal ligament(PDL) cells supplemented with 10ng/ml of $TGF-{\beta}_1$, 20ng/ml of PDGF-BB, 1ng/ml $TNF-\alpha$, or $1{\mu}g/ml$ LPS by western blot analysis. The results of this study were as follows ; 1. The expression of CH-4S was stronger in pulp, PDL, osteoblasts, osteoclasts and osteocytes in experimental group than in control group, but was rare in dentin, and cementum of experimental groups, regardless of the duration of force application, which was not different from that of control group. 2. In experimental group, the expression of CH-4S in pulp began to increase at 1 day after force application and got to the highest degree at 7 days. After 14 days, the expression in CH-4S immunoreactivity was decreased, and became similar to that of control group at 28 days. 3. The expression of CH-4S in PDL was noted in adjacent to alveolar bone. PDL showed higher intensity of immunolabelling after 1 day of orthodontic tooth movement. And the expression was more stronger in the tension side than that of pressure side of PDL at 1 day, but more stronger in the pressure side than that of tension side of PDL at 4 days. After 7 days, a decrease in CH-4S expression was observed. 4. The expression of CH-4S in alveolar bone got to the highest degree at 4 days, and At 7 days, a decrease in CH-4S expression was observed. 5. PDGF-BB notably raised the expression of CH-4S in the PDL cells at 3 days of cultivation 6. The expression of CH-4S of PDL cells was decreased with the application of $TNF-\alpha$ at 1 day. 7. Admixture of $TGF-{\beta}_1$ and PDGF-BB got more expression of CH-4S in PDL as compared to only $TGF-{\beta}1$ or PDGF-BB. A similar decrease of the expression of CH-4S was observed in the case of application of LPS or $TNF-\alpha$.

• The korean journal of orthodontics
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• v.29 no.1 s.72
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• pp.83-94
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• 1999

The purpose of this study was to evaluate the changes of cancellous and cortical bone and the effect of estrogen in ovariectomized rats. Fifty female rats, 250gm in body weight, were divided into three groups : ovariectomized group(OVE), ovariectomized and estrogen-injected group(OVE-EST), and sham operated and estrogen-injected group(EST). Bilateral ovariectomy was performed at the onset of the experiment. In OVE-EST group and EST group, estrogen was injected $50{\mu}g/kg$ B.W. every other days from 3 weeks after surgery to sacrifice. Each five rats were sacrificed after 5, 6, 7 weeks. One side of mandibular body was radiographed with a soft x-ray apparatus(Hitex Co., Ltd., Japan). Thereafter the obtained microradiographs were used for the morphometric analysis using a Image analyzer. The morphometric analysis was perforrmed for parameters such as total bone area, cortex bone area and medullary bone area. The other side of the mandibular bone was decalcified and embedded in paraffin as using a general method. The specimens were sectioned and stained with Mallory's anilline blue and observed light microscopically. The results were as follows. 1 In all groups, the proportion of cortex to total bone area was not significantly different. 2. In ovariectomized(OVE) group, the proportion of marrow cavity to medullary bone area increased significantly from 5 to 7 weeks(p<0.05). In ovariectomized and estrogen-injected(OVE-EST) group, it decreased significantly at 7 weeks, and in estrogen-injected(EST) group, it decreased significantly from 6 weeks(p<0.05). 3. Microradiogram and histopathologic findings revealed that marrow cavity was enlarged and osteoclasts were observed around irregular bone surface in OVE group. In OVE-EST group, the size of marrow cavity at 7 weeks was similar to that of control group. In EST group, as dense trabecular bone increased from 5 to 7 weeks, marrow cavity decreased.

• Journal of the korean academy of Pediatric Dentistry
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• v.27 no.2
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• pp.309-317
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• 2000

Bisphosphonates inhibit bone resorption in vivo and in vitro. Currently proposed mechanism of action of bisphosphonates involves both direct effect on osteoclasts and indirect effect through the mediation of osteoblasts. Recent understanding of molecular mechanism of osteoclastogenesis indicates that osteoclast differentiation is quite tightly regulated by signaling molecules from differentiating osteoblasts. Therefore this investigation was designed to elucidate the effect of bisphosphonate on osteoblast differentation. For this purpose, in vitro effects of etidronate and alendronate on the expression of Cbfa1 a master control gene of osteoblast differentiation, several bone marker genes, and formation of calcified nodules were evaluated. To evaluate the effect of bisphosphonate on calcified nodule formation, osteoblasts isolated from rat calvaria were cultured in a-MEM containing $10^{-4},\;10^{-5},\;10^{-6}M$ of etidronate or $10^{-6},\;10^{-7},\;10^{-8}M$ of alendronate for 15 days, and then stained by alizarin red to determine mineralization. To evaluate the effect of bisphosphonate on osteoblast differentiation, osteoblast cells were cultured in a-MEM containing $10^{-4},\;10^{-5},\;10^{-6}M$ of etidronate or $10^{-6}$ M of alendronate for 8 days. And then total RNA was extracted and northern blot analysis was done to examine the expression of Cbfa1, type I collagen, alkaline phosphatase, osteopontin and osteocalcin. The results were as follows: 1. Etidronate suppressed the calcification of bone nodule in dose dependent manner, while alendronate didn't. 2. The expression of Cbfa1 was decreased dose dependently by etidronate, but increased by alendronate. 3. Etidronate suppressed the expression of type I collagen, osteopontin and osteocalcin in dose dependent manner however alendronate promote the expression of osteoblast marker gene. 4. The expression of alkaline phosphatase was not affected either etidronate nor alendronate. These results suggest that etidronate suppressed the expression of Cbfa1 in dose dependent manner, and consequently the expression of osteoblast marker genes, such as type I collagen, osteopontin and osteocalcin were also suppressed in similar manner. And finally this decreased expression of osteoblastic marker gene prevent calcined bone nodule formation.

• Journal of the korean academy of Pediatric Dentistry
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• v.36 no.4
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• pp.625-630
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• 2009

Root resorption of primary teeth usually occurs as the succeeding permanent teeth erupt, which induces differentiation of the hemopoietic cells into osteoclasts. Their root resorption pattern reflects the eruption path of the succeeding permanent teeth, and eventually the primary teeth shed as their succeeding permanent teeth erupt. Even when a permanent tooth germ is congenitally missing, root resorption of the corresponding primary tooth may still occur due to various factors, such as inflammation, traumatic occlusal force, and weakness of periodontium etc. Such congenital missing of permanent teeth is a commonly observed phenomenon in human be ing, and it often accompanies delayed retention of primary teeth. The etiologic factors for congenital missing in elude not only systemic diseases, but also local factors and human evolution process. In the radiographs of the cases in this report, the primary teeth without succeeding permanent teeth show pathologic root resorption. Root resorption progressed about 1/2~3/4 of the roots, and the surfaces of the resorption area were irregular. Considering high susceptibility of the periodontal ligament of primary teeth to root resorption, pathologic root resorption of primary teeth with delayed retention can be explained by the increased masticatory muscle force and abnormal occlusion developed during the mixed dentition. When the primary teeth without succeeding permanent teeth are lost, decision for space maintenance is required and long-term treatment plan for further prosthetic or orthodontic treatment should be establsihed.

• The korean journal of orthodontics
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• v.33 no.4 s.99
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• pp.279-291
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• 2003

Electric current is a highly probable way as a clinical tool for tooth movement. The purposes of this study were to determine the usefulness of exogenous electric currents in accelerating orthodontic tooth movement and to investigate the effects of electric-orthodontic treatment on the remodeling of the periodontal tissue histologically The study was performed with six male cats weighing around 3kg. The electric device wich is providing the direct electric current of $20{\mu}A$ was inserted to the removable appliance. The right and left maxillary canines were assigned as control and experimental sides respectively. The control canine was Provided with orthodontic force (75gm) oかy and the experimental side was given the same amount of force and electricity. The lingual buttons were bonded to the maxillary canines and both sides of canines were retracted with NiTi coil spring. The electric device was adjusted to provide 20uh direct current to the experimental canines S hours a day The amount of the canine movement was measured with electronic caliper every week. After 4 weeks of tooth movement, the animals were sacrificed and the histologic study was performed. The results of this study were as follows. 1. The application of a direct current to the experimental tooth significantly increased the final amount of orthodontic tooth movement. The amount of tooth movement after 28-day was 37% more in the experimental side. 2. The electrically stimulated tooth showed histologic evidence of significant increases in the amount of bones and matrix deposition in the area of tension. 3. In the compression side, the electric-orthodontic treatment stimulated bone resorption more extensively in the experimental canines. 4. After 28 days of electricity exposure and orthodontic force, the experimental side demonstrated significantly more osteoblasts, osteoclasts, capillaries and osteoid tissues, reflectinr an increase in the local tissue's cellular activity. 5. Intermittent electrical stimulation (five hours a day) had effects to enhance orthodontic tooth movement and tissue remodeling. These results suggested that the low-intensity exogenous electric current by the miniature electric device might accelerate orthodontic tooth movement and bone remodeling in vivo and have the possibility to reduce the orthodontic treatment duration.