• BMB Reports
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• v.51 no.5
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• pp.230-235
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• 2018

Bone resorption by multinucleated osteoclasts is a multistep process involving adhesion to the bone matrix, migration to resorption sites, and formation of sealing zones and ruffled borders. Macrophage colony-stimulating factor (M-CSF) and osteopontin (OPN) have been shown to be involved in the bone resorption process by respective activation of integrin ${\alpha}v{\beta}3$ via "inside-out" and "outside-in" signaling. In this study, we investigated the link between signal modulators known to M-CSF- and OPN-induced osteoclast adhesion and spreading. M-CSF- and OPN-induced osteoclast adhesion was achieved via activation of stepwise signals, including integrin ${\alpha}v{\beta}3$, $PLC{\gamma}$, $PKC{\delta}$, and Rac1. Osteoclast spreading induced by M-CSF and OPN was shown to be controlled via sequential activation, consistent with the osteoclast adhesion processes. In contrast to osteoclast adhesion, osteoclast spreading induced by M-CSF and OPN was blocked via activation of $PLC{\gamma}/PKC{\alpha}/RhoA$ signaling. The combined results indicate that osteoclast adhesion and spreading are selectively regulated via $PLC{\gamma}/PKC{\alpha}-PKC{\delta}/RhoA-Rac1$ signaling.

• Journal of Korean Dental Science
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• v.8 no.2
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• pp.74-81
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• 2015

Purpose: In osteoclast differentiation, actin-rich membrane protrusions play a crucial role in cell adhesion. Odontogenic ameloblast-associated protein (Odam) contributes to cell adhesion by inducing actin rearrangement. Odam-mediated RhoA activity may play a significant role in multinucleation of osteoclasts. However, the precise function of Odam in osteoclast cell adhesion and differentiation remains largely unknown. Here, we identify a critical role for Odam in inducing osteoclast adhesion and differentiation. Materials and Methods: The expression of Odam in osteoclasts was evaluated by immunohistochemistry. Primary mouse bone marrow and RAW264.7 cells were used to test the cell adhesion and actin ring formation induced by Odam. Result: Odam was expressed in osteoclasts around alveolar bone. Odam transfection induced actin filament rearrangement and cell adhesion compared with the control or collagen groups. Overexpression of Odam promoted actin stress fiber remodeling and cell adhesion, resulting in increased osteoclast fusion. Conclusion: These results suggest that Odam expression in primary mouse osteoclasts and RAW264.7 cells promotes their adhesion, resulting in the induction of osteoclast differentiation.

• Biomolecules & Therapeutics
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• v.24 no.1
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• pp.9-18
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• 2016

Bone matrix is properly maintained by osteoclasts and osteoblasts. In the tumor microenvironment, osteoclasts are increasingly differentiated by the various ligands and cytokines secreted from the metastasized cancer cells at the bone metastasis niche. The activated osteoclasts generate osteolytic lesions. For this reason, studies focusing on the differentiation of osteoclasts are important to reduce bone destruction by tumor metastasis. The N-myc downstream-regulated gene 2 (NDRG2) has been known to contribute to the suppression of tumor growth and metastasis, but the precise role of NDRG2 in osteoclast differentiation induced by cancer cells has not been elucidated. In this study, we demonstrate that NDRG2 expression in breast cancer cells has an inhibitory effect on osteoclast differentiation. RAW 264.7 cells, which are monocytic preosteoclast cells, treated with the conditioned media (CM) of murine breast cancer cells (4T1) expressing NDRG2 are less differentiated into the multinucleated osteoclast-like cells than those treated with the CM of 4T1-WT or 4T1-mock cells. Interestingly, 4T1 cells stably expressing NDRG2 showed a decreased mRNA and protein level of intercellular adhesion molecule 1 (ICAM1), which is known to enhance osteoclast maturation. Osteoclast differentiation was also reduced by ICAM1 knockdown in 4T1 cells. In addition, blocking the interaction between soluble ICAM1 and ICAM1 receptors significantly decreased osteoclastogenesis of RAW 264.7 cells in the tumor environment. Collectively, these results suggest that the reduction of ICAM1 expression by NDRG2 in breast cancer cells decreases osteoclast differentiation, and demonstrate that excessive bone resorption could be inhibited via ICAM1 down-regulation by NDRG2 expression.

• Journal of Physiology & Pathology in Korean Medicine
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• v.27 no.4
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• pp.431-436
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• 2013

Bone homeostasis is maintained by co-ordination of bone-resorbing osteoclasts and bone-forming osteoblasts. Imbalance between osteoclasts and osteoblasts leads to many bone diseases such as osteoporosis, rheumatoid arthritis. Taxillus chinensis is a herb that has been widely used to improve bone health. However, the effect and mechanism of Taxillus chinensis extract on osteoclast differentiation and bone resportion has been unknown. Thus, We investigated the effect of Taxillus chinensis on expression of receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL)-induced osteoclast differentiation and bone resorption. Also, the action of Taxillus chinensis on mechanisms relating to osteoclast differentiation was studied. In this results, we identified that Taxillus chinensis significantly inhibited RANKL-induced osteoclast differentiation and bone resportion. Moreover, Taxillus chinensis was suppressed the activation of NF-${\kappa}B$ in bone marrow macrophage treated RANKL and M-CSF. Taxillus chinensis was down-regulated the mRNA expression of c-Fos, nuclear factor of activated T-cells (NFAT)c1, osteoclast-associated receptor (OSCAR), tartrate-resistant acid phosphatase (TRAP). The cell adhesion-related molecules such as integrin ${\alpha}v$ and integrin ${\beta}3$, and the filamentous actin (F-actin) rings of mature osteoclasts-related molecules such as dendritic cell-specific transmembrane preotein (DC-STAMP) and cathepsin K are also suppressed. Taken together, these results indicated that Taxillus chinensis will be a good candidate to treat osteoclast-mediated bone diseases.

• BMB Reports
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• v.52 no.11
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• pp.659-664
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• 2019

Vav1 is a Rho/Rac guanine nucleotide exchange factor primarily expressed in hematopoietic cells. In this study, we investigated the potential role of Vav1 in osteoclast (OC) differentiation by comparing the ability of bone marrow mononuclear cells (BMMCs) obtained from Vav1-deficient ($Vav1^{-/-}$) and wild-type (WT) mice to differentiate into mature OCs upon stimulation with macrophage colony stimulating factor and receptor activator of nuclear kappa B ligand in vitro. Our results suggested that Vav1 deficiency promoted the differentiation of BMMCs into OCs, as indicated by the increased expression of tartrate-resistant acid phosphatase, cathepsin K, and calcitonin receptor. Therefore, Vav1 may play a negative role in OC differentiation. This hypothesis was supported by the observation of more OCs in the femurs of $Vav1^{-/-}$ mice than in WT mice. Furthermore, the bone status of $Vav1^{-/-}$ mice was analyzed in situ and the femurs of $Vav1^{-/-}$ mice appeared abnormal, with poor bone density and fewer number of trabeculae. In addition, Vav1-deficient OCs showed stronger adhesion to vitronectin, an ${\alpha}_v{\beta}_3$ integrin ligand important in bone resorption. Thus, Vav1 may inhibit OC differentiation and protect against bone resorption.

• Journal of Microbiology and Biotechnology
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• v.11 no.5
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• pp.727-738
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• 2001

Macrophagal polykaryocytes (MPs) are terminally differentiated multinuclear macrophage cells responsible for remodeling and resorption of bone, foreign body, and tissue deposition in inflammation. MPs are encountered only in bone and cartilagenous tissues, in which they are referred to as osteoclasts, odontoclasts, in which they are referred to as osteoclasts, odontoclasts, and septoclasts. Depending on the disease, the MPs differentiate into many morphological variants that include foreign-body giant cells, Langhans-type cells, and Touton-type cells. Morphological heterogeneity of MPs could Touton-type cells. Morphological heterogeneity of MPs could reflect the giant cell formation from phenotypically different marophage precursors by the process of fusion. At present, many cytokines, adhesion/fusion molecules, and other factors of the microenvironment have been discovered that influence the multinucleation process. Many evidences suggest that conditions in giant cell fibrohistiocytomas, which facilitate MP formation, are similar to the inflammation site of granulomatosis. MPs in the giant cell tumors and granulomatosis foci are formed in response to the factors secreted by mesenchymal cells. It is proposed that one of the first steps in vertebrate evolution could be the organization of skeleton remodeling, in which osteoclasts play a major role. In this step, the same mechanism of regulations served as a basis for the development of both osteoclast and inflammatory forms of MPs.

• Restorative Dentistry and Endodontics
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• v.22 no.2
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• pp.575-595
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• 1997

Replacement resorption is followed by the delayed replantation of an avulsed tooth. Currently no effective treatment is substantiated for replacement resorption. The purpose of this study was to investigate the effect of stannous fluoride, bisphosphonate (etidronate disodium) and gallium nitrate, which have been shown to reduce dentin resorption, on human dentin. Osteoclasts were collected from tibeas of chick embryo. The cells were well agitated to prevent adhesion and seeded onto the sliced human dentin wafers which had been soaked in either culture media (control), or several different concentrations of stannous fluoride, etidronate disodium (l-hydroxyethylidene -1,1-bisphosphonate disodium), and gallium nitrate. Resorption was measured by counting the number of resorptive pit produced by the cells. Results are as follows. Stannous fluoride and etidronate disodium showed statistically significant reduction of dentin resorption(p<0.05) but the effect of stannous fluoride seemed to be its high cytotoxicity. Etidronate disodium did not show cytotoxicities in all experimented concentrations. Gallium nitrate did not show differences in resorption either between different concentrations or from the control group.