• Title, Summary, Keyword: Osteoclast

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Recombinant Human Parathyroid Hormone Related Peptide (1-34) Stimulates Osteoclastic Bone Resorption in Both Rodent and Avian Disagsresated Osteoclast Culture (파골세포배야에서 나타난 부갑상선호르몬의 설치류 및 조류 파골세포에 대한 촉진 효과)

  • 양대석;김일찬남궁용이창호
    • The Korean Journal of Zoology
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    • v.37 no.2
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    • pp.255-261
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    • 1994
  • Recombinant human pBrathyriod hormone related peptide (1-341 (rhPTHrP) has been known to stimulate bone resorption in intact bone tissue culture system. Osteoclast has been known as a primary responsible cell for bone resorption. To examine the effect of rhPTHrP on this cell, we employed disaggregated rat osteodast culture. As a result, we found that rhPTHrP sisnificBntly elevates both the number and total area of resorbed pits in this culture. On the other hand, the conflicting results between disagsregated rat osteoc13st culture and Ca2+-deficient hen osteoclast culture system have been a big obstacle for the progress of bone research. To verify the differences between rat 3nd chick osteoclast system, we performed the same experiment using chick embryonic osteoclast. Since the similar results were obtained from the disaggregated chick osteoclast culture, the discrepancy between chick and rat osteoclast culture study seemed to be due to the difference in culture method, rather due to the species-difference.

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Selective regulation of osteoclast adhesion and spreading by PLCγ/PKCα-PKCδ/RhoA-Rac1 signaling

  • Kim, Jin-Man;Lee, Kyunghee;Jeong, Daewon
    • 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.

Osteoclast Differentiation Factor Engages the PI 3-kinase, p38, and ERK pathways for Avian Osteoclast Differentiation

  • Kim, Hong-Hee;Kim, Hyun-Man;Kwack, Kyu-Bum;Kim, Si-Wouk;Lee, Zang-Hee
    • 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.

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Effects of Baicalin on the differentiation and activity of preosteoclasts

  • Ko, Seon-Yle
    • International Journal of Oral Biology
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    • v.34 no.2
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    • pp.81-86
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    • 2009
  • Baicalin is a flavonoid purified from the medicinal plant Scutellaria baicalensis. It has been reported that baicalin exhibits antibacterial, anti-inflammatory and analgesic effects. The present study was undertaken to determine the underlying cellular mechanisms of baicalin action in preosteoclasts. The effects of this flavonoid on preosteoclasts were determined by measuring osteoclast generation and osteoclast activity in macrophage-colony stimulating factor (M-CSF)-dependent bone marrow cells (MDBMCs) and in co-cultures of MDBMCs and osteoblasts. Osteoclast generation was assayed by measuring the number of tartrateresistant acid phosphatase (TRAP) (+) multinucleated cells after culture. Osteoclast activity was assayed by measuring the area of the resorption pit after culture. We found that osteoclast generation was induced by M-CSF and receptor activator of NF-kB ligand (RANKL), and by the 1.25-dihydroxycholecalciferol in our cultures. Baicalin decreased both osteoclast generation and activity in MDBM cultures and co-cultures indicating that it may inhibit bone resorption.

Rolipram, a Phosphodiesterase 4 Inhibitor, Stimulates Osteoclast Formation by Inducing TRANCE Expression in Mouse Calvarial Cells

  • Cho, Eun-Sook;Yu, Ja-Heon;Kim, Mi-Sun;Yim, Mi-Jung
    • Archives of Pharmacal Research
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    • v.27 no.12
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    • pp.1258-1262
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    • 2004
  • Phosphodiesterase (PDE) 4 is an enzyme that degrades intracellular cAMP. In the present study, the effect of rolipram, a specific phosphodiesterase (PDE) 4 inhibitor, on osteoclast formation was investigated. Rolipram induced osteoclast formation in cocultures of mouse bone marrow cells and calvarial osteoblasts. This activity was not observed in the absence of calvarial osteoblasts, suggesting that calvarial osteoblasts are likely target cells of rolipram. Osteoclast formation by rolipram was completely blocked by the addition of osteoprotegerin (OPG), a soluble decoy receptor for the osteoclast differentiation factor, TNF-related activation-induced cytokine (TRANCE, identical to RANKL, ODF, and OPGL). Northern blot analysis revealed the effect of rolipram to be associated with the increased expression of TRANCE mRNA in mouse calvarial osteoblasts. Collectively, these data indicate that PDE4 inhibitor up-regulates the TRANCE mRNA expression in osteoblasts, which in turn controls osteoclast formation.

Regulatory Effects of Cyclic AMP on Osteoclast Formation (조골세포내 cAMP 농도 변화가 파골세포 형성에 미치는 영향)

  • Chun Yunna;Yim Mijung
    • YAKHAK HOEJI
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    • v.49 no.1
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    • pp.109-113
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    • 2005
  • In the present study treatment of IBMX, a phosphodiesterase (PDE) inhibitor, alone induced osteoclast formation in co-cultures of mouse bone marrow cells and calvarial osteoblasts. However, treatment of IBMX in combination with prostaglandin $E_2\;(PGE_2)$ inhibited osteoclast formation in a dose-dependent manner. Among various isozyme-specific PDE inhibitors, a PDE4 specific inhibitor, rolipram, showed similar effects as IBMX on osteoclast formation. To address the involvement of cyclic adenosine monophosphate (cAMP) in osteoclast formation, cAMP concentration in calvarial osteoblasts was investigated. When calvarial osteoblasts were co-cultured with IBMX alone or in combination with $PGE_2$, the patterns of cAMP concentration in calvarial osteoblasts were differ each other suggesting that cAMP in calvarial osteoblasts subtly regulates osteoclast formation.

The IRF2BP2-KLF2 axis regulates osteoclast and osteoblast differentiation

  • Kim, Inyoung;Kim, Jung Ha;Kim, Kabsun;Seong, Semun;Kim, Nacksung
    • 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.

Effect of Sochungryong-tang Extract on Osteoclast Differentiation and Bone-pit Formation (소청룡탕이 파골세포 분화억제와 골흡수에 미치는 영향)

  • Ahn, Min-Youn;Lim, Hyung-Ho
    • The Journal of Korean Medicine
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    • v.38 no.3
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    • pp.59-72
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    • 2017
  • Objectives: This study was performed to evaluate effects of Sochungryong-tang Extract(SRE) on osteoclast differentiation and bone resorptionin order to find out the possibility for clinical use in preventing and treating osteoporosis. Methods: To evaluate the effect of SRE on osteoclast differentiation, we induced RAW 264. 7 cells to be differentiated to osteoclasts by RANKL (receptor activator of nuclear $factor-{\kappa}B$ ligand). We measured effect on TRAP (Tartrate-resistant acid phosphatase), NFATc, cathepsin K, MMP-9, inflammation related factors, histogenesis factors and bone resorption. Results: SRE decreased osteoclast differentiation, and also decreased expression of bone resorbing factors such as MMP-9, cathepsin K, TRAP, NFATc1, MITF, c-Fos, osteoclast stimulatory transmembrane protein, calcitonin receptor in RANKL-induced osteoclast. SRE also decreased Cyclooxygenase-2, indusible nitric oxide synthase, $TNF-{\alpha}$, which are thought to be related with the inflammatory bone destruction. Conclusion: SRE inhibits osteoclast differentiation and bone resorption. The results indicate that the BHT extract can potentially be applied for preventing and treating osteoporosis.

Fine Needle Aspiration Cytology of Osteoclast-like Giant Cell Tumor of the Liver (간의 파골세포모양 거대세포 종양의 세침흡인 세포학적 소견)

  • Park, Chan-Sik;Kim, Ji-Eun;Chang, Mee-Soo
    • 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.

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Gene Profiling in Osteoclast Precursors by RANKL Using Microarray

  • Lee, Na Kyung
    • 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.