• Biomedical Science Letters
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• v.19 no.2
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• pp.164-167
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• 2013

Osteoclasts are originated from hemopoietic progenitors of the monocyte/macrophage lineage and resorb mineralized tissues. Elevated osteoclast numbers and activity result in bone disease such as osteoporosis, Paget's disease, and tumor osteolysis. In order to identify the genes that are involved in osteoclast differentiation, microarray was performed after treated with RANKL for 12 h and 24 h in osteoclast precursors. The genes that changed by RANKL treatment were grouped by biological process or molecular function. Among them, the number of genes involved in signal transduction and nucleic acid binding was 6065 and 3066, respectively. When analyzed the number of genes changed more than 1.5 fold in the cells treated with RANKL for 12 h or 24 h compared to when RANKL was not treated, 83 and 62 genes were up-regulated; 56 and 62 genes were downregulated, respectively. To verify the microarray results, real-time RT-PCR for Cxcl1 and Slfn1genes that have not been reported yet related to osteoclast differentiation, as well as Ccl2 gene associated with osteoclast differentiation were carried out. Both experiments showed a similar result of more than 1.5 fold induction of these genes by RANKL treatment. These results suggest the possibility that Cxcl1 and Slfn1 may associate with osteoclastogenesis and provide that microarray is a useful tool to analyze the profile of genes changed during osteoclast differentiation by RANKL. Moreover, this gene profile contributes to understand the regulatory mechanisms involved in osteoclast differentiation and the pathogenesis, thus developing therapeutics of bone diseases such as osteoporosis.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.1
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• pp.23-26
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• 2010

The vascular changes in periodontal tissues cause local hypoxia which seems to affect the periodontal tissue cells. Abrupt changes in oxygen availability within the periodontium have been suggested to have a regulatory role in alveolar bone remodeling during tooth movement, bone growth or fracture healing. The purpose of this study was to study the effects of hypoxia on formation of osteoclast responsible for bone resorption, in vitro. Primary mouse bone marrow cells were cultured in normoxic (20% $O_2$) and hypoxic (1% $O_2$) conditions and assayed for cellular proliferation. The results obtained were as follows : 1. Reducing oxygen tension increased the formation of multinucleated osteoclasts. 2. Hypoxic stimulus increased the size of mature osteoclasts.

• The Journal of the Korean dental association
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• v.9 no.4
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• pp.191-194
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• 1971

The authors have studied cytomorphologically on the gian cells appearing in the giant cell lesions which had been collected from the biopsies at the department of oral pathology, college of dentistry, Seoul National University. The results are as follows: 1. We can classify two types of giant cells and large sized giant cells which have foamy, large nuclei and prominent nucleoli, and small sized giant cells which have small, round and homogenous stained cytoplasm. 2. We can not see the phagocytosed materials, only can see the foamy microvacuoles in the cytoplasm of giant cells. 3. We can not see the mitotic figures, nore fused figures in giant cells. 4. Osteoclasts in the periphery of bone tissue reveal large and pale stained with H-E stain, giant cells on the granulation tissue and chronic inflammatory tissue reveal deeply stained with hematoxylin and prominent nuclei, but smaller than osteoclasts.

• Journal of Physiology & Pathology in Korean Medicine
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• v.24 no.5
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• pp.848-853
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• 2010

Bone maintains its homeostasis through balance between bone resorbing osteoclasts and bone forming osteoblasts. Thus, unusual balance between osteoclasts and osteoblasts leads to pathological bone diseases, such as osteoporosis, rheumatoid arthritis, autoimmune arthritis, periodontitis. Schisandra chinensis well known traditional herbal has been used for treatment of diseases in China, Korea, Japan, andothers. Recently, research studies have demonstrated that the lignans found in Schisandra chinensis stimulate osteoblasts and suggest that it may be helpful against osteoporosis. However, the inhibitory effect of water extract of Schisandra chinensis on osteoclast differentiation remains largely unknown. In this study, Water extract of Schisandra chinensis markedly suppressed RANKL-induced osteoclast differentiation in cultures of BMMs without cytotoxicity. The mRNA expression of c-Fos, NFATc1, and TRAP induced by RANKL was inhibited by water extract of Schisandra chinensis. It also suppressed c-Fos and NFATc1 protein expression. Taken together, these results suggest that water extract of Schisandra chinensis has the potential to serve as a treatment of bone disease such as osteoporosis.

• 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.

• Journal of Society of Preventive Korean Medicine
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• v.19 no.2
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• pp.135-144
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• 2015

Objective : Saengmaek-san (SM) has been commonly used in Korea to treat various diseases that involve the respiratory and cardiovascular system. However, to date, the mechanism underlying the effects of osteoclasts differentiation of SM has not been clearly understood. Method : To evaluate the effect of SM on osteoclast differentiation, we induced RAW 264.7 cells to be differentiated to osteoclasts by RANKL, and we performed RT-PCR to measure gene expression. Results : SM decreased the number of TRAP(+) MNCs in RANKL-induced osteoclast. SM decreased the expression of MMP-9, cathepsin K1, TRAP, NFATc1, MITF, and COX-2 in the osteoclast. But SM increased the expression of iNOS, $TNF-{\alpha}$ and IL-6 in osteoclast. Conclusion : It is concluded that SM might decrease the bone resorption resulted from decrease of osteoclast differentiation and it's related gene expression.

• Journal of Periodontal and Implant Science
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• v.26 no.4
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• pp.859-872
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• 1996

The purpose of this study was to evaluate the effect of low concentrative ${\beta}-APN$ on the periodontal ligament and relationship between lathyrintic bodies and osteoclast cells near the by alveolar bone. Mandibles including teeth and periodontiums of 24 Sprague-Dawley rat was used. ${\beta}-APN$ 0.2g/kg/day soluted in mineral water was administrated for 5 days before sacrifice in experimental group. 3 rats on each day was sacrificed on 1, 3, 7, 11 days after stop administration ${\beta}-APN$. Histologic examination and the activity of osteoclasts by tartrate resistant acid phosphatase was observed. The results were as follows : 1. In experimental group, the The small foci of lathyrintic bodies surrounded by palisading fibroblasts were seen obviously on 1, 3 days and decreased after 7 days. On 11 days, fibroblasts of periodontal ligament similar to control group. 2. The lathyrintic bodies were seen in the middle zone of periodontal ligament of pressured area like furcation area, alveolar crest, bone resorption area than tensioned area of apposition area. 3. In experimental group of 1, 3 days, lathyrintic bodies were much seen in the area that osteoclasts was much distributed area. After 7 days, experimental group was seen the control group. In conclusion, rathyrintic bodies were formed by low concentrative ${\beta}-APN$ chiefly on the pressured area like furcation area, alveolar crest, bone resorption area than tensioned area of apposition side in periodontal tissue and concerned with osteoclast cells.

• BMB Reports
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• v.34 no.5
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• pp.421-427
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• 2001

Osteoclasts, cells primarily involved in bone resorption, originate from the hematopoietic precursor cells of the monocyte/macrophage lineage and differentiate into multinucleated mature forms. We developed an in vitro osteoclast culture system using embryonic chicken bone marrow cells. This culture system can be utilized in studies on the differentiation and function of osteoclasts. Phosphatidylinositol 3-kinase (PI3-kinase) and mitogen-activated protein kinases (MAPKs) have been implicated in diverse cellular functions including proliferation, migration, and survival. Using the developed avian osteoclast culture system, we examined the involvement of these kinases in osteoclast differentiation by employing specific inhibitors of the kinases. We Found that the inhibition of the PI 3-kinase, p38, or ERK interfered with osteoclast formation, suggesting that the signaling pathways that involve these molecules participate in the process of chicken osteoclast differentiation.

• BMB Reports
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• v.50 no.3
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• pp.150-155
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• 2017

Non-small-cell lung cancer (NSCLC) is the third most common cancer that spreads to the bone, resulting in osteolytic lesions caused by hyperactivation of osteoclasts. Activating mutations in epidermal growth factor receptor-tyrosine kinase (EGF-TK) are frequently associated with NSCLC, and afatinib is a first-line therapeutic drug, irreversibly targeting EGF-TK. However, the effects of afatinib on osteoclast differentiation and activation as well as the underlying mechanism remain unclear. In this study, afatinib significantly suppressed receptor activator of nuclear factor ${\kappa}B$ (RANK) ligand (RANKL)-induced osteoclast formation in bone marrow macrophages (BMMs). Consistently, afatinib inhibited the expression of osteoclast marker genes, whereas, it upregulated the expression of negative modulator genes. The bone resorbing activity of osteoclasts was also abrogated by afatinib. In addition, afatinib significantly inhibited RANKL-mediated Akt/protein kinase B and c-Jun N-terminal kinase phosphorylation. These results suggest that afatinib substantially suppresses osteoclastogenesis by downregulating RANK signaling pathways, and thus may reduce osteolysis after bone metastasis.

• International Journal of Oral Biology
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• v.30 no.4
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• pp.135-141
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• 2005

Although it has been known that TGF-${\beta}1$ acts as a crucial cofactor in osteoclast differentiation, its mode of action is still unclear. In the present study, we studied the effect of TGF-${\beta}1$ on the differentiation of osteoclast depending on the developmental stages. Murine bone marrow cells were induced to differentiate into mature osteoclasts in the presence of receptor activator of NF-${\kappa}B$ ligand (RANKL) and macrophage colony stimulating factor (M-CSF). In the early stage of the differentiation TRAP(-) mononuclear precursor cells were obtained from nonadherent M-CSF dependent bone marrow cells, which further differentiated into mature osteoclasts. TGF-${\beta}1$ stimulated osteoclast differentiation, which was stronger when cells were stimulated by TGF-${\beta}1$ in the early stage than the later differentiation. TGF-${\beta}1$ increased the expression of RANK and synergistically stimulated RANKL-induced activation of NF-${\kappa}B$ MAP kinase in TRAP(-) mononuclear precursor cells. These results suggest that activation of osteoclast differentiation by TGF-${\beta}1$ may be ascribed to the both increased expression and activation of RANK in the osteoclast differentiation, especially in the early stage of differentiation.