• Molecules and Cells
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• v.38 no.1
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• pp.75-80
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• 2015

Osteoclasts are unique cells responsible for the resorption of bone matrix. MicroRNAs (miRNAs) are involved in the regulation of a wide range of physiological processes. Here, we examined the role of miR-26a in RANKL-induced osteoclastogenesis. The expression of miR-26a was upregulated by RANKL at the late stage of osteoclastogenesis. Ectopic expression of an miR-26a mimic in osteoclast precursor cells attenuated osteoclast formation, actin-ring formation, and bone resorption by suppressing the expression of connective tissue growth factor/CCN family 2 (CTGF/CCN2), which can promote osteoclast formation via upregulation of dendritic cell-specific transmembrane protein (DC-STAMP). On the other hand, overexpression of miR-26a inhibitor enhanced RANKL-induced osteoclast formation and function as well as CTGF expression. In addition, the inhibitory effect of miR-26a on osteoclast formation and function was prevented by treatment with recombinant CTGF. Collectively, our results suggest that miR-26a modulates osteoclast formation and function through the regulation of CTGF.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.6
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• pp.539-546
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• 1999

Bone is a complex tissue in which resorption and formation continue throughout life. The bone tissue contains various types of cells, of which the bone forming osteoblasts and bone resorbing osteoclasts are mainly responsible for bone remodeling. Periodontal disease represents example of abnormal bone remodeling. Osteoclasts are multinucleated cells present only in bone. It is believed that osteoclast progenitors are hematopoietic origin, and they are recruited from hematopoietic tissues such as bone marrow and circulating blood to bone. Cells present in the osteoclast microenvironment include marrow stromal cells, osteoblasts, macrophages, T-lymphocytes, and marrow cells. These cells produce cytokines that can affect osteoclast formation. In vitro model systems using bone marrow cultures have demonstrated that $IL-l{\beta},\;IL-3,\;TNF-{\alpha},$ bFGF can stimulate the formation of osteoclasts. In contrast, IL-4 inhibits osteoclast formation. Knowledge of cytokines and bFGF that affect osteoclast formation and their capacity to modulate the bone-resorbing process should provide critical insights into normal calcium homeostasis and disorders of bone turnover such as periodontal disease, osteoporosis and Paget's disease.

• BMB Reports
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• v.45 no.5
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• pp.281-286
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• 2012

Osteoclasts are multinucleated cells that are formed by the fusion of pre-fusion osteoclasts (pOCs). The fusion of pOCs is known to be important for osteoclastic bone resorption. Here, we examined the effect of IFN-${\gamma}$ on the fusion of pOCs. IFN-${\gamma}$ greatly increased the fusion of pOCs in a dose-dependent manner. Furthermore, IFN-${\gamma}$ induced pOC fusion even in hydroxyapatite-coated plates used as a substitute for bone. The resorption area of pOCs stimulated with IFN-${\gamma}$ was significantly higher than that of the control cells. IFN-${\gamma}$ induced the expression of dendritic cell-specific transmembrane protein (DC-STAMP), which is responsible for the fusion of pOCs. IFN-${\gamma}$ enhanced DC-STAMP expression in a dose-dependent manner. The mRNA expression of c-Fos and nuclear factor of activated T cells (NFAT) c1 was enhanced in the pOCs treated with IFN-${\gamma}$. Taken together, these results provide a new insight into the novel role of IFN-${\gamma}$ on the fusion of pOCs.

• Journal of Nutrition and Health
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• v.24 no.1
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• pp.30-39
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• 1991

This study was designed to investigate the effects of dietary calcium. serum estrogen level and physical activity on the bone status of 116 healthy elderly women living in urban area. Current calcium intake was assessed by convenient method(refered to as Ca intake) and calcium containing food frequency method(refered to as Ca index) Daily activity record was used for the estimation of physical activity level, and serum estrogen level was measured from fasting blood of subjects. The rate of bone resorption was evaluated by the determination of hydroxyproline(Hpr) in fasting urine with correction for creatinine excretion. The results of this study are summarized as follows : 1) Average daily Ca intake of subjects was 621.4$\pm$155.8mg, which is above the Korean recommended dietary allowances. However 44.8% of the subjects consumed Ca below RDA level. Ca index score was significantly correlated with the bone status(P<0.05), Ca intake did not show significant correlation with the bone status although a positive trend of influence was evident. 2) Average serum estrogen level of subjects was 18.7$\pm$9.8pg Contrary to our anticipation. estrogen level did not show any significant relation to age and bone status. 3) Daily physical activity was classified into four categories by activity intensity : sedentary. moderate, active and severe. The average physical activity of subjects belong to moderate level. and the bone status was significantly related to the physical activity(P<0.01) 4) Among other influential factors such as age, pocket-money. family type. drinking, smoking and BMI, there was a significant difference between bone status and BMI(P<0.05). 5) Multiple regression analysis of variables showed that physical activity has greater effect than other variables when the entire subjects were taken into account. However. eliminating the subjects whose bone status rated as excellent(Hpr/cr<0.009), Ca index showed higher correlation than physical activity. These results have demonstrated that dietary calcium intake is the primary important factor for keeping good bone health and that bone status of subjects with a sufficient calcium intake is affected by various factors such as physical activity, age, smoking. BMI and others.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.19 no.1
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• pp.35-44
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• 1997

The most critical factor in determining which type of implant to be used would be the available bone of the patient. Usually a minimum of 5mm in the bone width and 8mm in the bone height is necessary to ensure primary implant stability and maintain the integrity of bone contact surface. Placement of implant is limited by the several anatomic strutures such as maxillary sinus, floor of the nose, inferior alveolar neurovascular bundle and nasopalatine foramen, etc. When severe resorption of alveolar ridge is encountered, implant placement would be a problematic procedure. A number of techniques to improve the poor anatomic situations have been proposed. This article reports 4 cases of patients using surgical procedures such as blade implant technique, cortical split technique in the anterior maxillary area, sinus lifting and lateral repositioning of inferior alveolar nerve, We treated dental implant candidates with unfavorable alveolar ridge utilizing various surgical techniques, resulted in successful rehabilitation of edentulous ridge.

• Journal of Periodontal and Implant Science
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• v.37 no.4
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• pp.743-753
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• 2007

Purpose: The purposes of this study were to compare and quantify the expression of MMP-3, $PGE_2$ and IL-6 in the gingival tissues of patients with $type_2$ diabetes mellitus and healthy adults with chronic periodontitis. Material and methods: Gingival tissue samples were obtained during periodontal surgery or tooth extraction. According to the patient's systemic condition & clinical criteria of gingiva, each gingival sample was devided into three groups. Group 1(n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from systemically healthy 8 patients. Group 2(n=8) is inflamed gingiva from patients with chronic periodontitis. Group 3(n=8) is inflamed gingiva from patients with chronic periodontitis associated with type 2 DM. Tissue samples were prepared and analyzed by Westernblotting. The quantification of MMP-3, $PGE_2$ and IL-6 were performed using a densitometer and statistically analyzed by one-way ANOVA followed by Tukey test. Results: 1. The expression levels of MMP-3 were shown highest in group 3 compared to group 1 and 2, and It showed increasing tendency in group 2 and 3. 2. The expressions of $PGE_2$ and IL-6 were shown increasing tendency in group 2 and 3, and It was highest in group 3. 3. As expressions of MMP-3 were increased, $PGE_2$ and IL-6 expressions showed increasing tendency in group 3 than group1 and 2, although there were no proportional relationship. Conclusion: This study demonstrated that the expression levels of MMP-3, $PGE_2$ and IL-6 will be inflammatory markers of periodonta linflamed tissue and DM. It can be assumed that MMP-3 affect to expressions of $PGE_2$ and IL-6 in progression of periodontal inflammation with alveolar bone resorption to type 2 DM.

• Journal of Periodontal and Implant Science
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• v.51 no.4
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• pp.264-275
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• 2021

Purpose: Periodontitis is considered a local risk factor for medication-related osteonecrosis of the jaws (MRONJ). However, little is known about the progression of periodontitis in the presence of zoledronic acid (ZOL). The aim of this study was to evaluate the effects of the systemic use of ZOL on the progression of experimental periodontitis (EP) in rats, as ZOL could modulate the progression of periodontitis and concomitantly cause MRONJ in individuals with periodontitis. Methods: Forty-eight male Wistar rats were randomly distributed in 6 groups (n=8 each). To induce EP, ligatures were placed around the right first mandibular molars. Three groups were treated with ZOL (0.15 mg/kg/week, intraperitoneal), and 3 with 0.9% saline solution (controls). In the ZOL/Lig30 and ZOL/Lig 15 groups, after 4 weeks of treatment with ZOL, EP was induced and euthanasia was performed after 30 and 15 days of EP induction, respectively. In both groups, the animals continued to receive ZOL after EP until the end of the experiment. In the Lig/ZOL group, EP was induced first, and 15 days later, ZOL was administered for 8 weeks, with euthanasia 1 week after the last dose. After euthanasia, the mandibles were evaluated using micro-computed microtomography (micro-CT) and histomorphometry. Bone loss was measured, and the presence of osteonecrosis was evaluated histologically. The data were evaluated using the Student t-test and the Mann-Whitney test, with a significance level of 5%. Results: In the Lig/ZOL group, micro-CT revealed less alveolar bone resorption in the distal root (P<0.01) than in the control group (Lig/Con). Histomorphometric analysis confirmed less alveolar bone resorption in the Lig/ZOL group (P=0.001). Histologically, osteonecrosis was more common in the ZOL groups. Conclusion: ZOL decreased alveolar bone resorption in rats with EP. However, it presented a higher risk for MRONJ.

• Journal of Nutrition and Health
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• v.42 no.4
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• pp.309-317
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• 2009

As far as we know, there were no studies of the effect of L-arginine on bone metabolism in post-menopausal women or ovariectomized rats. The primary objective of the current study was to determine whether arginine supplementation was associated with alterations in femoral and spinal bone mineral density (BMD) and bone markers in ovariectomized (Ovx) rats. Forty female Sprague-Dawley rats were divided into two groups, Ovx and sham groups, which were each randomly divided into two subgroups that were fed control and arginine supplemented diet. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. Bone resorption was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Serum osteocalcin, growth hormone, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH) and calcitonin were analyzed using radioimmunoassay kits. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur. The serum and urine concentrations of Ca and P were determined. The plasma was analyzed for arginine. Diet did not affect weight gain, mean food intake, and plasma arginine concentration. Urinary Ca excretion was decreased by arginine supplementation in Ovx rats, but statistically not significant. The Ovx rats fed arginine-supplemented diet were not significantly different in ALP, osteocalcin, crosslinks value, PTH, calcitonin and IGF-1 compared to those fed control diet. The arginine-supplemented group had significantly higher serum Ca and growth hormone than control group. Spine and femur BMD were significantly increased by arginine supplementation on 5th and 9th weeks after feeding. Our findings indicate that dietary L-arginine supplementation decreased bone mineral density loss in Ovx rats. Therefore, dietary arginine supplementation may represent a potentially useful strategy for the management of osteoporosis.

• Journal of Nutrition and Health
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• v.36 no.5
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• pp.452-458
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• 2003

Soybean is a rich source of isoflavones such as genistein and daidzein. Soy isoflavones have both weak estrogenic and anti-estrogenic effects and are structurally similar to tamoxifen, an agent that has an effect similar to that of estrogen in terms of reducing postmenopausal bone loss. The purpose of this study was to determine the effects of differences in protein source (casein vs soy) and isoflavone levels (reduced vs higher levels) on selected bone markers and hormones in growing male rats. Thirty weanling Sprague-Dawley young rats were divided into 3 groups: The control group was fed a casein-based diet, the soy concentrate group was fed soy protein with totally reduced isoflavones content (isoflavones 0.07 mg/g protein), and the soy isolate group was fed soy protein with a higher than normal isoflavones content (isoflavones 3.4 mg/g protein). The degree of bone formation was estimated by measuring serum osteocalcin and alkaline phosphoatase (ALP). By determining collagen cross-linkage by immunoassay and correcting with creatinine values, the bone resorption rate was compared. Serum osteocalcin, growth hormone, estrogen and calcitonin were analyzed using radio immunoassay kits. The bone formation marker and ALP activity were differentiated by protein source, showing higher values than casein in feeding either soy isolate or soy concentrate. In this study using growing rats, the differences in isoflavone contents were not a significant factor in either bone formation or bone reaborption markers. Moreover, the soy isolate group had significantly higher levels of growth hormone than the casein group. The findings of this study suggest that growth hormone is partially responsible for its bone-formation effects in young growing rats. Soy protein and the isoflavones in soy protein are beneficial for bone-formation in growing male rats. Therefore, exposure to soy protein and isoflavones early in life may have long-term health benefits in preventing bone diseases such as osteoporosis. Further study to evaluate the mechanism of action of isoflavones on bones is warranted. (Korean J Nutrition 36(5): 452∼458, 2003)

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.23 no.1
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• pp.27-44
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• 1993

This study was performed to investigate the changes of mandibular condyle by low calcium diet and the effects of irradiation on the bone in osteoporotic state. In order to carry out this experiment, 80 seven-week old Sprague-Dawley strain rats weighing about 150 gm were selected and equally divided into one experimental group of 40 rats and one control group with the remainder. The experimental group and the control group were then subdivided into two group and exposed to irradiation. The two irradiation groups received a single dose of 20 Gy on the jaw area only and irradiated with a cobalt-60 teletherapy unit. The rats in the control and experimental groups were serially terminated by fours on the 3rd, the 7th, the 14th, and the 21st day after irradiation. After termination, both sides of the dead rats mandibular condyle were removed and fixed with 10% neutral formalin. The bone mineral density of mandibular condyle was measured by use of dual energy X-ray bone densitometer(model DDX-alpha, Lunn Corp., U. S. A.). The mandibular condyle was radiographed with Hitex HA-80(Hitex Co., Japan). Thereafter, the obtained radiographs were observed, and the mandibular condyle was further decalcified and embedded in paraffin as the general method. The specimen sectioned and stained with hematoxylin-eosin, PAS and Rabbit Anti-Human Tumor Necrosis Factor-a observed by a light microscope. The obtained results were as follows: 1. In the non-irradiated group with the low calcium diet, the bone mineral density of the condyle was markedly decreased after 14 days, and decrease the number of trabeculae of the condyle and resorption of the calcified cartilaginous zone were observed after 3 days. On microscopic observations, the number nd size of trabeculae were decreased after 7 days of experiment. 2. In the irradiated group with the low calcium diet, the bone mineral density of the condyle was markedly decreased after 14 days and resorption of the calcified cartilaginous zone and decrease the number and coarse of the trabeculae of the condyle were observed. These findings were extended rather than in non-irradiated group with low calcium diet. On microscopic observations, many osteoclasts were detected and the number and size of trabeculae were somewhat decreased after 7 days. Also there was degenerative changes of tissues of bone marrow on the 14th day but that condition was restored on the 21st day of experiment. 3. In the irradiated group with normal diet, the bone mineral density of the condyle was somewhat decreased with times and degree of decrease of the number of trabeculae was somewhat larger than in the non-irradiated group with normal diet. On microscopic observations, the tissues of bone marrow were atrophic and degenerative changes but that condition was restored on the 21st day of experiment. 4. In immunocytochemical findings, in the irradiated and non-irradiated groups with low calcium diet, negative or partial positive response to TNF was observed, but positive response in the normal diet groups.