• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.1
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• pp.24-32
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• 2007

The odontogenic keratocyst(OKC) is a common developmental odontogenic cyst and represents approximately 11% of odontogenic cysts. It is decided by microscopic and histopathologic determinant rather than by clinical appearance. In this study, expression of RANKL and OPG in OKC in relation to age and gender of patient and recurrence, location of lesion were examined through immuno- histochemical study. The RANKL and OPG antibody staining were used. The obtained result were as follow. 1. Positive immunoreactivity to RANKL/OPG in all specimens was found. 2. There was no significant difference in immunohistochemical expression of RANKL relating to recurrence, location of OKCs and age, gender of patients. 3. There was no significant difference in immunohistochemical expression of OPG relating to recurrence, location of OKCs and age, gender of patients. From above results, it is suggested that activation of osteoclasts by RANKL is an important mechanism by which OKCs cause bone destruction.

• Journal of Periodontal and Implant Science
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• v.37 no.4
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• pp.849-857
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• 2007

Purpose: The purposes of this study were to compare and quantify the expressions of RANK and RANKL in the gingival tissues of non-periodontitis patient and patients with chronic periodontitis, in order to understand the contribution of these proteins to periodontal destruction. 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 divided into two groups. Group 1 (n=8) is clinically healthy gingiva without bleeding and no evidence of bone resorption or periodontal pockets, obtained from non-periodontitis patients. Group 2 (n=8) is inflammed gingiva from patients with chronic periodontitis. Tissue samples were prepared and analyzed by Western blotting. The quantification of RANK and RANKL were performed using a densitometer and statistically analyzed by Student's t-Test. Results: The expression of RANK were similar in group 1 and 2. The difference between group 1 and 2 was not statistically significant. And the mean amount of RANKL was more increased in group 2 than group 1. The difference between group 1 and group 2 was statistically significant. Conclusion: The expression level RANK didn't show any significant difference between healthy tissue from non-periodontitis patients and inflamed tissue from chronic periodontitis, but the expression level of RANKL in inflammed tissue from chronic periodontitis showed significantly increased tendency compared to healthy gingiva from non-periodontitis patients. Therefore, characteristics of RANK and RANKL in progress of chronic periodontitis would be basis of further studies in diagnostic method and treatment index of the disease.

• Journal of Physiology & Pathology in Korean Medicine
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• v.26 no.4
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• pp.506-510
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• 2012

Bone homeostasis is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Osteoporosis, rheumatoid arthritis and periodontal disease are related with up-regulated osteoclast formation and its activity. Gol-Swae-Bo(Drynariae Rhizoma) is widely used on skeletal disease. In this study, we sought to examine the effect of Drynariae Rhizoma in RANKL-induced osteoclast differentiation. The extract of Drynariae Rhizoma inhibited RANKL-induced osteoclast differentiation in a dose dependent manner without cytotoxicity. receptor activator of nuclear factor-${\kappa}B$ ligand(RANKL) mediated $I{\kappa}B$ degradation in bone marrow macrophages(BMMs). However, the extract of Drynariae Rhizoma inhibited RANKL induced $I{\kappa}B$ degradation in BMMs. And mRNA expression of OSCAR, TRAP, c-Fos and NFATc1 was suppressed by the extract of Drynariae Rhizoma. Moreover, the extract of Drynariae Rhizoma inhibited the protein expression of NFATc1 and c-Fos induced by RANKL. After all the analysis, these results suggest that Drynariae Rhizoma may be good candidate of medicine in the treatment of bone-related disease.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.2
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• pp.135-147
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• 2019

Objectives This study was performed to evaluate the effect of Pyrola japonica extract (NJ) and its principal constituent, homoarbutin (HA) on osteoclast differentiation and gene expression and bone resorption. The osteoclastogenesis and gene expression were determined in receptor activator of nuclear factor kappa B ligand (RANKL)-stimulated RAW264.7 cell. Methods In order to evaluate the effect of HA extracted from NJ on bone resorption, osteoclasts were used to be differentiated and formed by stimulating RAW264.7 cells with RANKL. Tartarate-resistant acid phosphatase (TRAP) (+) polynuclear osteoclast formation ability was evaluated, and differentiation control genes including cathepsin K, matrix metalloproteinases-9 (MMP-9), and TRAP in osteoclast differentiation were analyzed by real-time polymerase chain reaction (PCR). Immunoblotting was performed to measure the effect of mitogen-activated protein kinase (MAPK) factors on bone resorption, and the effect of osteoclasts on osteoclast differentiation was measured. Results Both NJ and high concentration of HA blocked RANKL-stimulated differentiation from RAW264.7 cell to TRAP-positive multinucleated cells. NJ reduced RANKL-induced expression of TRAP, cathepsin K. Both NJ and high concentration of HA inhibited RANKL-mediated expression of MMP-9, nuclear factor of activated T-cells, cytoplasmic 1, and cellular Jun-fos. NJ suppressed RANKL-stimulated expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, tumor necrosis factor-alpha, and levels of interleukins. Both NJ and HA decreased bone resorption in osteoclast-induced bone pit formation model. Conclusions These results suggest that NJ and HA blocked bone resorption by decreasing RANKL-mediated osteoclastogenesis through down-regulation of genes for osteoclast differentiation.

• Korean Journal of Exercise Nutrition
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• v.23 no.1
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• pp.13-20
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• 2019

[Purpose] The OPG/RANK/RANKL signaling is a new family of bone metabolism biomarkers belonging to the immune system. However, the bone metabolism response to long-term exercise in the RANKL/RANK/OPG signaling is less evident. The purpose of this study was to examine these biomarkers in healthy college females after 12-weeks combined exercise intervention. [Methods] Participants (N=22, 22.4±1.3yrs) were randomly divided in two different group: 12 in the control group and 10 in the exercise group performing combined exercise program that interventions was conducted 3 times per week for 12 weeks. The outcome measures included serum concentrations of RANKL, OPG and bone metabolic cytokines such as TNF-α and IL-6, and mRNA expressions of same variables from PBMC. VO_2max and bone mineral density (BMD) were measured at before and after exercise intervention. [Results] There were no significant differences in the serum RANKL, OPG concentrations and all RANKL/RANK/OPG signaling mRNA expression on interaction effect between group and time (NS). Also no significant differences were found in the serum TNF-α and IL-6 concentrations and mRNA expression (NS). The IL-6 mRNA expression only showed significant difference in the main effect of groups (p<.05). There were also no significant differences in the VO_2max and BMD on interaction effect between group and time (NS). [Conclusion] These results suggested that there were no effects on bone mineral density and RANKL/RANK/OPG signaling without the effect of 8-weeks combined exercise on cardiovascular endurance fitness.

• YAKHAK HOEJI
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• v.53 no.2
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• pp.78-82
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• 2009

We explored the effects of dexamethasone on osteoclast precursors using BMMs. Dexamethasone inhibited the proliferation of BMMs. Furthermore, it stimulated the osteoclast formation via NFATc1 activation in the presence of RANKL. Since dexamethasone targeted the early stage of osteoclast formation, we investigated its effect on mRNA expression of GR and $IFN-{\beta}$. Whereas dexamethasone had no effects on GR expression in the presence of RANKL, it reduced the expression of $IFN-{\beta}$, suggesting that dexamethasone increased RANKL-induced osteoclast formation by modulating $IFN-{\beta}$.

• Korean Journal of Pharmacognosy
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• v.48 no.2
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• pp.155-159
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• 2017

Cudrania tricuspidata Bureau (Moraceae) is a traditional oriental medicine that has been widely used as anti-oxidant, anti-inflammatory and immunomodulatory in Korea. This study was performed that the 70% ethanol extract of the roots of C. tricuspidata (CTE) suppressed receptor activator of NF-${\kappa}B$ ligand (RANKL)-induced osteoclastogenesis, actin ring formation in RAW 264.7 cell lines. CTE significantly inhibited the JNK/mitogen-activated protein kinase (MAPK) signaling pathway without affecting ERK and p38 signaling in RANKL-stimulated RAW 264.7 cells. Also, CTE inhibited RANKL-induced expression of c-Fos, an upstream activator of NFATc1. Consequently, CTE suppresses osteoclast differentiation by inhibiting RANKL induced MAPK signaling pathways and disrupts the actin rings in mature osteoclasts. Thus, CTE can be used for the development of osteoporosis treatment drug with a natural material.

• Journal of Physiology & Pathology in Korean Medicine
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• v.22 no.4
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• pp.796-801
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• 2008

Bone is a dynamic tissue that is regulated by the balance between bone-resorbing osteoclasts and bone-forming osteoblasts. Curcumin isolated from Kang-hwang (Turmeric) is widely used as a foodstuff, cosmetic, and medicine. However, the effect of curcumin isolated from Kang-hwang in osteoclast differentiation remains unknown. In this study, we sought to examine the role of curcumin in osteoclast differentiation. Here we show that curcumin greatly inhibited RANKL-mediated osteoclast differentiation in osteoclast precursors without cytotoxicity. RANKL induced the phosphorylation of p38 and JNK mitogen-activated protein kinase (MAPK) and mediated $I-{\kappa}B$ degradation in bone marrow macrophages (BMMs). However, RANKL-mediated p38 MAPK phosphorylation was inhibited by the addition of curcumin. Curcumin inhibited the mRNA expression of TRAP, c-Fos, and NFATc1 in BMMs treated with RANKL. Furthermore, the protein expression of c-Fos and NFATc1 induced by RANKL was suppressed by curcumin treatment. Taken together, our results suggest that curcumin may have a potential therapeutic role in bone-related diseases such as osteoporosis by inhibiting osteoclast differentiation.

• The Journal of Internal Korean Medicine
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• v.38 no.6
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• pp.1035-1048
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• 2017

Objectives: This study was performed to investigate the effects of Gardenia jasminoides extract (GJ) on osteoclast differentiation and bone resorption in vitro. Methods: To investigate the effect of GJ on osteoclast differentiation, the mouse leukemic myeloid cell line RAW 264.7 was stimulated by RANKL (receptor activator of nuclear factor kB ligand). Osteoclast differentiation was measured by counting TRAP (+) MNC in the presence of RANKL. To elucidate the mechanism of the inhibitory effect of GJ on osteoclast differentiation, gene expression of TRAP, Cathepsin K, MMP-9, NFATc1, c-Fos, MITF, DC-STAMP, CTR, OC-STAMP and Atp6v0d2 was measured using reverse transcription-PCR (RT-PCR). Bone resorption was measured using the bone pit formation assay. Results: GJ decreased the number of TRAP (+) MNCs in the presence of RANKL. GJ inhibited the expression of cathepsin K, MMP-9, TRAP, MITF, NFATc1, c-Fos, iNON, OC-STAMP, Atp6v0d2, and DC-STAMP in the osteoclast, and inhibited bone pit formation in vitro. Conclusions: The results suggest that GJ has inhibitory effects on bone resorption resulting from inhibition of osteoclast differentiation and gene expression.

• BMB Reports
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• v.44 no.7
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• pp.473-477
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• 2011

Periodontitis is a very prevalent disease. Therefore, biomarkers for the early and standard diagnoses of periodontitis are urgently needed. TACE is a membrane-bound metalloprotease. Although a recent study suggested that TACE levels in GCF are elevated during periodontal disease, the levels of TACE in GCF at different stages of chronic periodontitis have not been determined. Here, we analyzed the protein levels of TACE in GCF from periodontal disease subjects and confirmed that the protein levels of TACE were higher in the moderate periodontitis groups. TACE is known to be a NF-${\kappa}B$ ligand that stimulates RANKL secretion in osteoblasts. To understand the effects of TACE on RANKL and OPG in osteoblasts, we treated MG63 cells with TACE. We observed an increase in RANKL protein expression but a decrease in OPG protein expression. Our data suggest that TACE can induce RANKL expression and promote osteoclastogenesis, thus worsening the outcome of periodontitis.