• The Korean Journal of Cytopathology
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• v.10 no.1
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• pp.79-84
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• 1999

Osteoclast-like giant cell tumor of the liver is an extremely rare malignancy with poor prognosis. To our knowledge, 5 cases have been reported in English literatures, but there was no report about fine needle aspiration cytologic(FNAC) features. We experienced a case of osteoclast-like giant cell tumor of the liver obtained by computed tomography(CT)-guided FNAC and needle biopsy. The cytologic findings mimicked slant cell tumor of the bone. A large hepatic mass of the left lobe with abdominal wall invasion was found by CT in a 46- year-old female complaining of epigastric pain. The FNAC showed moderately cellular smears consisting of osteoclast-like giant cells and mononuclear cells, which were individually scattered or intermingled in clusters. The osteoclast-like giant cells had abundant cytoplasms and multiple small round nuclei with fine chromatin and distinct nucleoli. The mononuclear cells had moderate amount of cytoplasm and relatively bland-looking oval nuclei with single small nucleoli. All of the cytologic features recapitulated the histologic findings of bland-looking osteoclast-like multinucleated giant cells evenly dispersed throughout the background of mononuclear cell. The immunohistochemical study showed positive reaction for CD68 and vimentin, but negative for cytokeratin in both osteoclast-like slant cells and mononuclear cells.

• Journal of Oral Medicine and Pain
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• v.25 no.1
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• pp.53-62
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• 2000

Bone marrow culture systems are widely used to differentiate osteoclast-like cells in vitro using several osteotropic hormones. In this study, we isolated and cultured the mouse bone marrow cells with or without some osteotropic hormones such as parathyroid hormone(PTH), prostaglandin $E_2(PGE_2)$ and $l,25(OH)_2-vitamin$ $D_3$(Vit. $D_3$). We confirmed the formation of osteoclast-like cells morphologically and functionally by the expression of tartrate-resistant acid phosphatase(TRAP) and by their capability to resorb dentin slices. We also studied the effects of transforming growth $factor-{\beta}(TGF-{\beta})$ and epidermal growth factor(EGF) on the Vit. $D_3-induced$ osteoclast-like cell formation. In control, a few multinucleated cells were formed whereas PTH and $PGE_2$ increased the number of multinucleated cells. PTH, $PGE_2$ and Vit. $D_3$ induced the formation of TRAP-positive multinucleated cells. After culture of mouse bone marrow cells on the dentin slices with or without osteotropic hormones, giant cells with diverse morphology were found on the dentin slices under the scanning electronmicroscopy. After removing the attached cells, resorption pits were identified on the dentin slices, and the shape of resorption pits was variable. EGF increased the osteoclast-like cell formation induced by Vit. $D_3$, however, $TGF-{\beta}$ showed biphasic effect, which at low concentration, increased and at high concentration, decreased the osteoclast-like cell formation induced by Vit. $D_3$.

• The Korean Journal of Cytopathology
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• v.18 no.1
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• pp.69-73
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• 2007

Mammary carcinoma with osteoclast-like giant cells is an unusual neoplasm characterized by giant cells, mononuclear stromal cells, and hemorrhage accompanying a low grade carcinoma. We present the cytological findings in a case of invasive ductal carcinoma with osteoclast-like giant cells that was initially confused with a fibroadenoma, due to its well-demarcated and soft mass and the young age of the patient. A 28-year-old female presented with a 4.5 cm, well demarcated, soft and nontender mass in the right breast. Fine needle aspiration cytology (FNAC) showed a combination of low grade malignant epithelial cell clusters and osteoclast-like giant cells. The atypical epithelial cells were present in cohesive sheets and clusters. Osteoclast-like giant cells and bland-looking mononuclear cells were scattered. An histological examination revealed the presence of an invasive ductal carcinoma with osteoclast-like giant cells. We report here the cytological findings of this rare carcinoma in a very young woman. The minimal atypia of the epithelial cells and its soft consistency may lead to a false negative diagnosis in a young woman. The recognition that osteoclastlike giant cells are rarely present in a low grade carcinoma, but not in benign lesion, can assist the physician in making a correct diagnosis.

• The korean journal of orthodontics
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• v.25 no.6 s.53
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• pp.697-704
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• 1995

Chicken calvarial bone is known to contain various cell types, but their exact composition is unknown. By characterizing the chicken calvarial bone biochemically, it can be used to study biochemical, histochemical actions of bone cells in general. Calvaria of 18-day-old white leg horn embryo was aseptically dissected and bone cell populations were isolated by sequential enzymatic digestion. Histochemical study for osteoclast-like bone cell. population was performed with tartrate resistant acid phosphatase(TRAP) stain and for osteoblast-like bone cell population, alkaline phosphatase(ALP) stain was performed. Biochemical study for osteoblast-like bone cell population was performed using alkaline phosphatase(ALP) assay. Following conclusions were obtained from this study. 1. TRAP positive multi and mononuclear cells were mostly observed in group I and II, indicating that osteoclast-like bone cell population is mostly found in these groups. 2. All the cultured groups showed almost equal ALP activities and were positive for ALP stain, indicating that osteoblast-like bone cell population is evenly dispersed in all culture groups. 3. Experimental group treated with $1,25(OH)_{2}D_3$ showed increase in ALP activity in contrast to the control group, confirming previous studies that $1,25(OH)_{2}D_3$ increases ALP activities in in vitro bone cultures. 4. Results from von Kossa's stain indicated that in vitro bone formation had occured after 3 weeks of culture with beta-glycero phosphate.

• The Journal of Korean Obstetrics and Gynecology
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• v.29 no.2
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• pp.66-82
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• 2016

Objectives : This study was conducted to evaluate the effect of Kanghwalsokdan-tang Gamibang water extract (KSG) on osteoporosis. Methods : RANKL-stimulated RAW 264.7 was used to evaluate inhibitory effect of KSG osteoclast differentiation and gene expression. We counted TRAP (+) multinucleated cells and measured TRAP activity and mRNA expressions of osteoclastogenesis-related genes (NFATc1, MITF, JNK1, cathepsin K, MMP-9) to figure out the effect of KSG on osteoclast. Osteoblastogenesis was also determined in rat calvarial cell. Alkaline phosphatase (ALP) activity, bone matrix protein and collagen synthesis were measured by using murine calvarial cell. Results : KSG inhibited the differentiation of osteoclast precursor cell and expression of genes related osteoclastogenesis like NAFTc1, MITF, c-fos, JNK1, Cathepsin K, MMP-9 and TRAP. KSG increased cell division and function of osteoblast separated from the skull of a rat and ALP synthesis, biosynthesis of bone matrix protein and collagen. Conclusions : Reviewing these results, KSG has efficacy on osteoclast inhibition and osteoblast activation. After further study, KSG will be able to apply for osteoporosis treatment and prevention.

• The korean journal of orthodontics
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• v.25 no.6 s.53
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• pp.715-722
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• 1995

Orthodontic tooth movement in response to orthodontic force results from actions of osteoclasts and osteeoblasts in the cell level. Convincing evidence has now been provided to support the view that osteoclasts are derived from mononuclear cells that originate in the bone marrow or other hematopoietic organs and they migrate to the bones via vascular routes. Nitric oxide(NO), which accounts for the biological properties of endothelium-derived relaxing factor(EDRF), is the endogenous stimulator of soluble guanylate cylase. The discovery of the formation of nitric oxide(NO) from L-arginine in mammalian tissues and its biological roles has, in the last 7 years, thrown new light onto many areas of research. Data from experiments in vitro showed that N-metyl-L-arginine(L-NMA) and L-nitro-L- arginine(L-NAME) are competitive inhibitors of nitric oxide synthase. This study suggest that the multinucleated cells in our culture have characteristics of osteoclasts and that the potential bone cell activity of nitric oxide in vitro may be mediated in part by stimulation of marrow mononuclear cells to form osteoclast-like cells. Bone marrow cells were obtaineed from tibia of 19-days old chick embryo. After sacrifice, tibia was quickly dissected and the bone were then split to expose the medullary bone. The cells were attached for 4 hours and the nonadherent cells were collected. Marrow cells weere cultured in 96-well plate in medium 199. To examine the number of TRAP-positive multinucleated cells(MNCs), $10^{-8}\;M\;Vit=D_3$ and various concentration of L-NMA and L-NAME weere added at the beginning of cultures and with each medium change. After 7 days of culture. tartrate-resistant acid phosphatase(TRAP) staining was performed for microscopic evaluation. Cells haying more than three nuclei per cell were counted as MNCs. The obsrved results were as follows;1. 1,25-dihydroxyvitamine $D_3$ stimulated the osteoclast-like multinucleated cells in cultures of chick embryo bone marrow. 2. Nitric oxide synthase inhibitors(NOSI ; N-NMA, N-NAME) stimulated the osteoclast-like cells in cultures of chick embry bone marrow. 3. 1,25-dihydroxyvitamine$D_3$ and nitric oxide synthase inhibitors did not appear to have additive effect on the generation of TRAP-positive MNCs. These results suggest that nitric oxide synthase inhibitors may stimulate the osteoclast-like multinucleated cell formation and fusion in cultures of chick bone marrow.

• The Korean Journal of Cytopathology
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• v.9 no.2
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• pp.221-225
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• 1998

Malignant tumors of the breast with stromal multinucleated giant cells are rare entity of uncertain clinical significance. There have been few reports on the fine needle aspiration cytologic(FNAC) findings about these rare tumors. We report a FNAC case of invasive mammary carcinoma with osteoclast-like giant cells not only for its rare occurrence but in particular for its distinctive cytologic picture on aspirated material. The patient was a 40-year-old woman who presented with a right breast mass for one month. Mammography showed a well-demarcated rounded mass density without calcification. The aspirates of FNAC were highly cellular and two main cell types were seen; malignant epithelial cells and osteoclast-like multinucleated giant cells. The carcinoma cells occurred singly or arranged in loose clusters with ill-defined cytoplasm, oval nuclei, coarse chromatin and small but distinct nucleoli. The multinucleated giant cells showed variable number of nuclei with prominent nucleoli and abundant dense oxyphilic cytoplasm. The immunocytochemical studies suggested that osteoclast-like giant cells were not of epithelial origin, but rather of histlocytic origin.

• International Journal of Oral Biology
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• v.31 no.2
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• pp.67-72
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• 2006

Nitric oxide(NO) is a labile, uncharged, reactive radical that functions as a sensitive mediator of intercellular communication in diverse tissues. It has been reported that NO is produced by osteoblast and these results may suggest that NO is integrally involved in the regulation of osteoclast formation and osteoclast resorption activity by osteoblastic cells. We examined the effect of cytokines on NO release by mouse bone marrow cell. We also examined the effects of cytokines and sodium nitroprusside(SNP) on the formation of osteoclast-like cell from mouse bone marrow cells in culture. Cytokines stimulated NO production of mouse bone marrow cells, and N-nitro-L-arginine methyl ester, a specific inhibitor of NO synthase, suppressed the cytokine-induced NO production. SNP showed dual action in the generation of osteoclasts. The addition of $30{\mu}M$ SNP inhibited the formation of tartrate resistant acid phosphatase(TRAP)(+) multinucleated cell, whereas lower concentration($3{\mu}M$) of SNP enhanced it. Although the precise action of NO remains to be elucidated in detail, the action of NO in osteoclast generation in our studies seems to be associated, at least in part, with bone metabolism and bone pathophysiology.

• BMB Reports
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• v.52 no.7
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• pp.469-474
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• 2019

Kruppel-like factor 2 (KLF2) has been implicated in the regulation of cell proliferation, differentiation, and survival in a variety of cells. Recently, it has been reported that KLF2 regulates the p65-mediated transactivation of $NF-{\kappa}B$. Although the $NF-{\kappa}B$ pathway plays an important role in the differentiation of osteoclasts and osteoblasts, the role of KLF2 in these bone cells has not yet been fully elucidated. In this study, we demonstrated that KLF2 regulates osteoclast and osteoblast differentiation. The overexpression of KLF2 in osteoclast precursor cells inhibited osteoclast differentiation by downregulating c-Fos, NFATc1, and TRAP expression, while KLF2 overexpression in osteoblasts enhanced osteoblast differentiation and function by upregulating Runx2, ALP, and BSP expression. Conversely, the downregulation of KLF2 with KLF2-specific siRNA increased osteoclast differentiation and inhibited osteoblast differentiation. Moreover, the overexpression of interferon regulatory protein 2-binding protein 2 (IRF2BP2), a regulator of KLF2, suppressed osteoclast differentiation and enhanced osteoblast differentiation and function. These effects were reversed by downregulating KLF2. Collectively, our data provide new insights and evidence to suggest that the IRF2BP2/KLF2 axis mediates osteoclast and osteoblast differentiation, thereby affecting bone homeostasis.

• Journal of Acupuncture Research
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• v.27 no.4
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• pp.99-114
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• 2010

Objectives : The purpose of this study is to observe the effects of RUBI FRUCTUS phamacopuncture infusion solution at $KI_{10}$ on osteoporotic Rats Induced by ovariectomy. Methods : The author performed several experimental items to analyze cytotoxic, osteoporosis evaluation, change of ALP, creatinine, Ca, P, osteocalcin, Ca/P ratio and histological change of serum and tibia. Results : 1. Creatinine and phosphorus in serum was decreased significantly in RF-HA than control group. 2. Calcium and phosphorus in tibia was increased significantly in RF-HA than control group. 3. Osteoclast like cell in tibia was increased significantly in control group, decreased significantly in RF-HA. 4. In the histological study in tibia, TBT was significantly increased, GPL was significantly decreased in the RF-HA than control group. Conclusions : This study suggested that RF-HA at KI10 has significant effect on osteoporosis.