• The Journal of Internal Korean Medicine
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• v.40 no.1
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• pp.58-69
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• 2019

Objective: This study investigated the effects of Hansu-Daebowon (HDW) on bone resorption in vitro and bone loss in vivo. Methods: Osteoclast differentiation was measured by counting TRAP (+) MNC formed from RAW 264.7 in the presence of RANKL. Bone pit formation was determined in an artificial bone slice loaded with RANKL-stimulated osteoclasts. To elucidate the mechanisms of the inhibitory effects of HDW on bone resorption and osteoclast differentiation, osteoclastogenic genes (i.e. TRAP, MMP-9, NFATc1, c-Fos, and Cathepsin K) were measured using real time PCR. Furthermore, bone loss was observed using micro-CT in an LPS-treated mammal model. Results: HDW inhibited the bone pit formation in vitro and inhibited bone loss in vivo. Moreover, HDW decreased the number of TRAP (+) MNCs in the presence of RANKL, and HDW inhibited the expressions of cathepsin K, MMP-9, TRAP, NFATc1, and c-Fos in the osteoclasts. Conclusion: HDW exerts inhibitory effects on bone loss and bone resorption resulting from the inhibitions of osteoclast differentiation and osteoclastogenic gene expression.

• Biomolecules & Therapeutics
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• v.28 no.4
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• pp.337-343
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• 2020

Activation of osteoclast and inactivation of osteoblast result in loss of bone mass with bone resorption, leading to the pathological progression of osteoporosis. The receptor activator of NF-κB ligand (RANKL) is a member of the TNF superfamily, and is a key mediator of osteoclast differentiation. A flavanone glycoside isolated from the fruit of Poncirus trifoliata, poncirin has anti-allergic, hypocholesterolemic, anti-inflammatory and anti-platelet activities. The present study investigates the effect of poncirin on osteoclast differentiation of RANKL-stimulated RAW264.7 cells. We observed reduced formation of RANKL-stimulated TRAP-positive multinucleated cells (a morphological feature of osteoclasts) after poncirin exposure. Real-time qPCR analysis showed suppression of the RANKL-mediated induction of key osteoclastogenic molecules such as NFATc1, TRAP, c-Fos, MMP9 and cathepsin K after poncirin treatment. Poncirin also inhibited the RANKL-mediated activation of NF-κB and, notably, JNK, without changes in ERK and p38 expression in RAW264.7 cells. Furthermore, we assessed the in vivo efficacy of poncirin in the lipopolysaccharide (LPS)-induced bone erosion model. Evaluating the micro-CT of femurs revealed that bone erosion in poncirin treated mice was markedly attenuated. Our results indicate that poncirin exerts anti-osteoclastic effects in vitro and in vivo by suppressing osteoclast differentiation. We believe that poncirin is a promising candidate for inflammatory bone loss therapeutics.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.16 no.9
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• pp.1906-1914
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• 2012

In this paper, relative service differentiation in JET based optical burst-switched networks with deflection routing is presented. It differs from conventional schemes in that it tries to make the loss rate of high class bursts as low as possible while maintaining the desired proportional ratio between the high class bursts and low class bursts. Strategies applied to it are dynamic wavelength allocation and the preemption which are combined to deflection routing. With dynamic wavelength allocation, the number of wavelengths allocated to high class bursts are dynamically changed. Preemption which gives more preference to high class bursts is also applied to decrease its loss rate. To lower the loss rate, deflection routing is applied for any kind of traffic. With those strategies, the suggested scheme shows desired properties that the loss rate of high class traffic is as lowered as possible. A queueing model for the scheme is developed to approximate loss ratio and the numerical results show that the proposed scheme provisions relative service differentiation.

• The Journal of Internal Korean Medicine
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• v.43 no.6
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• pp.1134-1148
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• 2022

Purpose: We evaluated whether Spatholobus suberectus extract (SSE) can be used as a means of preventing and treating osteoporosis by measuring its effect on osteoclast differentiation, gene expression, and bone resorption. Methods: SSE was used to examine the effect on RAW 264.7 cells stimulated with RANKL to induce bone resorption. The inhibitory effect of TRAP formation and the expression of the bone resorption factors TRAP, cathepsin K, and MMP-9 during differentiation were measured. The effects on the differentiation-related factors NFATc and TRAIL and on the expression of OC-STAMP, DC-STAMP, ATP6v0d2, MITF, c-Fos, and inflammation-related factors were also evaluated. The effect on bone resorption was evaluated by culturing RANKL-treated osteoclasts on artificial bone fragments and observing the resulting resorption traces. The effect on bone damage in experimental animals was also measured. Results: SSE inhibited the differentiation of RANKL-stimulated osteoclasts into osteoclasts and suppressed the expression of cathepsin K, TRAP, MMP-9, NFATc1, TRAIL, MITF, OC-STAMP, DC-STAMP, ATP6v0d2, and c-Fos genes. Bone pore formation due to osteoclast action was also inhibited, and LPS-induced bone loss was suppressed in animal experiments. Conclusions: SSE could be useful for the prevention or treatment of osteoporosis by inhibiting osteoclast differentiation and bone resorption and suppressing bone loss induced in experimental animals. However, studies of larger populations are required.

• Molecules and Cells
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• v.44 no.7
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• pp.444-457
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• 2021

Although the mechanism of chronic myeloid leukemia (CML) initiation through BCR/ABL oncogene has been well characterized, CML cell differentiation into erythroid lineage cells remains poorly understood. Using CRISPR-Cas9 screening, we identify Chromobox 8 (CBX8) as a negative regulator of K562 cell differentiation into erythrocytes. CBX8 is degraded via proteasomal pathway during K562 cell differentiation, which activates the expression of erythroid differentiation-related genes that are repressed by CBX8 in the complex of PRC1. During the differentiation process, the serine/threonine-protein kinase PIM1 phosphorylates serine 196 on CBX8, which contributes to CBX8 reduction. When CD235A expression levels are analyzed, the result reveals that the knockdown of PIM1 inhibits K562 cell differentiation. We also identify TRIM28 as another interaction partner of CBX8 by proteomic analysis. Intriguingly, TRIM28 maintains protein stability of CBX8 and TRIM28 loss significantly induces proteasomal degradation of CBX8, resulting in an acceleration of erythroid differentiation. Here, we demonstrate the involvement of the CBX8-TRIM28 axis during CML cell differentiation, suggesting that CBX8 and TRIM28 are promising novel targets for CML research.

• Annual Conference of KIPS
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• 2008.11a
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• pp.1332-1335
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• 2008

In order to various service types of real time and non-real time traffic with varying requirements are transmitted over the IEEE 802.16 standard is expected to provide quality of service(QoS) researchers have explored to provide a queue management scheme with differentiated loss guarantees for the future Internet. The sides of a packet drop rate, an each class to differential drop probability on achieving a low delay and high traffic intensity. Improved a queue management scheme to be enhanced to offer a drop probability is desired necessarily. This paper considers multiple random early detection with differential drop probability which is a slightly modified version of the Multiple-RED(Random Early Detection) model, to get the performance of the best suited, we analyzes its main control parameters (max_th, min_th, max_p) for achieving the proportional loss differentiation (PLD) model, and gives their setting guidance from the analytic approach. we propose Dynamic-multiple queue management scheme based on differential drop probability, called Dynamic-VQSDDP(Variable Queue State Differential Drop Probability)T, is proposed to overcome M-RED's shortcoming as well as supports static max_p parameter setting values for relative and each class proportional loss differentiation. M-RED is static according to the situation of the network traffic, Network environment is very dynamic situation. Therefore max_p parameter values needs to modify too to the constantly and dynamic. The verification of the guidance is shown with figuring out loss probability using a proposed algorithm under dynamic offered load and is also selection problem of optimal values of parameters for high traffic intensity and show that Dynamic-VQSDDP has the better performance in terms of packet drop rate. We also demonstrated using an ns-2 network simulation.

• Journal of Acupuncture Research
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• v.32 no.3
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• pp.27-40
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• 2015

Objectives : This study was performed to evaluate the effects of water extract of Cervi Parvum Cornu(CPC), Aconiti Lateralis Radix Preparata(ALR), and Yongbu-tang(YBT) on suppression of the receptor activator of nuclear factor kappa-B ligand(RANKL)-induced osteoclast differentiation and bone resorption. Methods : The effects of CPC, ALR, YBT extracts on osteoclast differentiation were determined by culture of bone marrow macrophage(BMM). The mRNA expression levels of the nuclear factor of activated T-cells cytoplasmic 1(NFATc1), c-Fos and tartrate-resistant acid phosphatase(TRAP) in BMMs were analyzed by reverse transcriptase polymerase chain reaction(RT-PCR). Similarly, the protein expression levels of NFATc1, c-Fos, mitogen-activated protein kinase(MAPK)s and ${\beta}$-actin in cell lysates were measured by western blotting. In addition, effects of CPC, ALR and YBT extracts were determined by means of Lipopolysaccharide(LPS)-induced bone-loss with mice. Results : CPC, ALR and YBT extracts showed remarkable inhibition on RANKL-induced osteoclast differentiation without cytotoxicity. CPC and ALR extracts significantly reduced the protein expression level of NFATc1. YBT extract significantly reduced the mRNA expression levels of c-Fos, NFATc1 and the protein expression levels of c-Fos, NFATc1, AKT, p38, c-Jun N-terminal kinase(JNK). Further, YBT extract suppressed degradation of$ I-{\kappa}B$. And ALR extract significantly restored the bone erosion by LPS treatment in mice. Conclusions : YBT extract showed more remarkable inhibition on osteoclast differentiation than CPC and ALR extracts in vitro. ALR extract showed remarkable inhibition on bone resorption in vivo. Thus, YBT extract can be a useful treatment for bone-loss diseases such as osteoporosis.

• BMB Reports
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• v.56 no.10
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• pp.545-550
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• 2023

Osteoporosis is a major public health concern, which requires novel therapeutic strategies to prevent or mitigate bone loss. Natural compounds have attracted attention as potential therapeutic agents due to their safety and efficacy. In this study, we investigated the regulatory activities of boeravinone B (BOB), a natural rotenoid isolated from the medicinal plant Boerhavia diffusa, on the differentiation of osteoclasts and mesenchymal stem cells (MSCs), the two main cell components responsible for bone remodeling. We found that BOB inhibited osteoclast differentiation and function, as determined by TRAP staining and pit formation assay, with no significant cytotoxicity. Furthermore, our results showing that BOB ameliorates ovariectomy-induced bone loss demonstrated that BOB is also effective in vivo. BOB exerted its inhibitory effects on osteoclastogenesis by downregulating the RANKL/RANK signaling pathways, including NF-κB, MAPK, and PI3K/Akt, resulting in the suppression of osteoclast-specific gene expression. Further experiments revealed that, at least phenomenologically, BOB promotes osteoblast differentiation of bone marrow-derived MSCs but inhibits their differentiation into adipocytes. In conclusion, our study demonstrates that BOB inhibits osteoclastogenesis and promotes osteoblastogenesis in vitro by regulating various signaling pathways. These findings suggest that BOB has potential value as a novel therapeutic agent for the prevention and treatment of osteoporosis.

• BMB Reports
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• v.45 no.10
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• pp.571-576
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• 2012

Radiotherapy is considered to cause detrimental effects on bone tissue eventually increasing bone loss and fracture risk. However, there is a great controversy on the real effects of irradiation itself on osteoblasts, and the mechanisms by which irradiation affects osteoblast differentiation and mineralization are not completely understood. We explored how X-ray radiation influences differentiation and bone-specific gene expression in mouse calvarial osteoblasts. Irradiation at 2 Gy not only increased differentiation and mineralization of the cells, but also upregulated the expression of alkaline phosphatase, type I collagen, osteopontin, and osteocalcin at early stages of differentiation. However, irradiation at higher doses (>2 Gy) did not stimulate osteoblast differentiation, rather it suppressed DNA synthesis by the cells without a toxic effect. Additional experiments suggested that transforming growth factor-beta 1 and runt-transcription factor 2 play important roles in irradiation- stimulated bone differentiation by acting as upstream regulators of bone-specific markers.

• Animal cells and systems
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• v.14 no.4
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• pp.283-289
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• 2010

Ssanghwa-tang (SHT) is a traditional Korean herbal medicine widely prescribed to decrease fatigue following an illness. The purpose of this study was to investigate the effects of SHT on osteoclast differentiation in vitro, and on bone loss in ovariectomized (OVX) rats in vivo. SHT significantly reduced the receptor activator for the nuclear factor ${\kappa}B$ (NF-${\kappa}B$) ligand (RANKL)-induced tartrate-resistant acid phosphatase (TRAP) activity, and multinucleated osteoclast formation in RAW264.7 cells without affecting cell viability. In addition, SHT significantly attenuated RANKL-induced mRNA expression levels of c-Src and cathepsin K. To examine the in vivo effect of SHT on OVX-induced bone loss in OVX rats, we administered SHT (0.6 g/kg BID) orally to OVX rats for 12 weeks. SHT administration significantly blocked OVX-induced decrease of femoral bone mineral density (BMD) and femoral trabeculae in OVX rats. In conclusion, these results suggest that SHT treatment effectively prevents OVX-induced bone loss, and this effect may result from its inhibitory effect on osteoclast differentiation.