• 대한한의학회지
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• 제27권1호
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• pp.229-239
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• 2006

Objectives : Articular cartilage is a potential target for drugs designed to inhibit the activity of matrix metalloproteinases (MMPs) to stop or slow the destruction of the proteoglycan and collagen in the cartilage extracelluar matrix. The purpose of this study was to investigate the effects of KHBJs for cartilage-protective effect in human and rabbit articular cartilage explants. Methods : The cartilage-protective effects of KHBJ were evaluated by using glycosaminoglycan degradation assay, collagen degradation assay, colorimetric analysis of MMPs activity, and histological analysis in rabbit and human cartilage explants culture. Results : KHBJs significantly inhibited GAG and collagen release of rabbit and human cartilage explant in a concentration-dependent manner. Also, KHBJs inhibited MMP-3 and MMP-13 activities from IL-$1{\alpha}$-treated cartilage explants cultures. Histological analysis indicated that KHBJ004 reduced the degradation of the cartilage matrix compared with that of IL-$1{\alpha}$-treated cartilage explants. KHBJ004 had no harmful effect on chondrocytes viability or cartilage morphology in cartilage explants. Conclusions : These results indicate that KHBJs inhibits the degradation of proteoglycan and collagen through the downregulation of MMP-3 and MMP-13 activities without affecting the viability or morphology of IL-$1{\alpha}$-stimulated rabbit and human articular cartilage explants.

• Biomolecules & Therapeutics
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• 제22권5호
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• pp.414-419
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• 2014

Matrix metalloproteinases (MMPs) are zinc-dependent endopeptidases that regulate cell-matrix composition and are also involved in processing various bioactive molecules such as cell-surface receptors, chemokines, and cytokines. Our group recently reported that MMP-3, -8, and -9 are upregulated during microglial activation and play a role as proinflammatory mediators (Lee et al., 2010, 2014). In particular, we demonstrated that MMP-8 has tumor necrosis factor alpha (TNF-${\alpha}$)-converting enzyme (TACE) activity by cleaving the prodomain of TNF-${\alpha}$ and that inhibition of MMP-8 inhibits TACE activity. The present study was undertaken to compare the effect of MMP-8 inhibitor (M8I) with those of inhibitors of other MMPs, such as MMP-3 (NNGH) or MMP-9 (M9I), in their regulation of TNF-${\alpha}$ activity. We found that the MMP inhibitors suppressed TNF-${\alpha}$ secretion from lipopolysaccharide (LPS)-stimulated BV2 microglial cells in an order of efficacy: M8I>NNGH>M9I. In addition, MMP inhibitors suppressed the activity of recombinant TACE protein in the same efficacy order as that of TNF-${\alpha}$ inhibition (M8I>NNGH>M9I), proving a direct correlation between TACE activity and TNF-${\alpha}$ secretion. A subsequent pro-TNF-${\alpha}$ cleavage assay revealed that both MMP-3 and MMP-9 cleave a prodomain of TNF-${\alpha}$, suggesting that MMP-3 and MMP-9 also have TACE activity. However, the number and position of cleavage sites varied between MMP-3, -8, and -9. Collectively, the concurrent inhibition of MMP and TACE by NNGH, M8I, or M9I may contribute to their strong anti-inflammatory and neuroprotective effects.

• 한국인터넷방송통신학회논문지
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• 제8권5호
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• pp.105-111
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• 2008

패킷 오버헤드 감소, 경로최적화, 핸드오프지연 그리고 핸드오프에 따른 신호량의 감소를 위해 이동망들에 대한 이동성 지원이 중요하다. MIPv6와 HMIPv6은 접근망에 관계없이 이동성을 제공하는 이동성관리프로토콜이다. 그러나 이들 기법은 핸드오프 발생으로 인하여 통신 품질이 크게 악화된다. MIPv6와 HMIPv6와 같은 기존의 이동성관리프로토콜에서 발생하는 핸드오프 성능을 개선시키기 위한 방안으로서, 본 논문은 FMIPv6와 버퍼링 기능을 지닌 확장된 HMIPv6를 결합한 핸드오프지연감소기법 (LLHS)을 제시하였다. 여기서 MAP은 핸드오프 발생시 이동 망 내에 이동 라우터나 이동 노드로 향한 패킷들을 버퍼링한다. 모의실험을 통하여 제안 기법이 전송 지연과 패킷 손실을 감소시킨다는 것을 보였다.

• Journal of Periodontal and Implant Science
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• 제35권1호
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• pp.21-30
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• 2005

Matrix metalloproteinases (MMPs) are a family of host-derived proteolytic enzymes and implicated in the remodeling and degradation of extracellular matrix under both physiological and pathological conditions. Connective tissue degradation in periodontal diseases is thought to be due to excessive MMP activities over their specific inhibitors. The effects of lipopolysaccharide (LPS) from Prevotella intermedia, one of the major putative pathogens of periodontitis, on the expression of mRNA for MMPs and tissue inhibitors of metalloproteinases (TIMPs) in human gingival and periodontal ligament fibroblasts were examined by reverse transcriptase-polymerase chain reaction (RT-PCR). The expression of mRNAs encoding MMP-1, -2, -3, -10, and -14 was increased in human gingival fibroblasts treated with p. intermedia LPS, whereas MMP-11 and TIMP-2 mRNA expression was decreased in these cells stimulated with LPS. P. intermedia LPS increased the MMP-1, -2, -10, -11, and -14 mRNA expression and decreased TIMP-1 and -2 mRNA expression in human periodontal ligament fibroblasts. These findings imply that P. intermedia LPS may play an important role in the connective tissue degradation in periodontitis.

• Nutrition Research and Practice
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• 제10권3호
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• pp.265-273
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• 2016

BACKGROUND/OBJECTIVES: The inhibitory effect of Hijikia fusiforme (HF) extracts on degenerative osteoarthritis was examined in primary cultured rat cartilage cells and a monosodium iodoacetate (MIA)-induced osteoarthritis rat model. MATERIALS/METHODS: In vitro, cell survival and the expression of matrix metalloproteinases (MMPs), collagen type I, collagen type II, aggrecan, and tissue inhibitor of metalloproteinases (TIMPs) was measured after $H_2O_2$ ($800{\mu}M$, 2 hr) treatment in primary chondrocytes. In vivo animal study, osteoarthritis was induced by intra-articular injection of MIA into knee joints of rats, and then RH500, HFE250 and HFE500 were administered orally once a day for 28 days. To determine the anti-inflammatory effects of HFE, nitric oxide (NO), prostaglandin $E_2$ ($PGE_2$) expression were measured. In addition, real-time PCR was performed to measure the genetic expression of MMPs, collagen type I, collagen type II, aggrecan, and TIMPs. RESULTS: In the in vitro assay, cell survival after $H_2O_2$ treatment was increased by HFE extract (20% EtOH). In addition, anabolic factors (genetic expression of collagen type I, II, and aggrecan) were increased by HFE extract (20% EtOH). However, the genetic expression of MMP-3 and 7, known as catabolic factors were significantly inhibited by treatment with HFE extract (20% EtOH). In the in vivo assay, anabolic factors (genetic expression of collagen type I, II, aggrecan, and TIMPs) were increased by oral administration of HFE extract. However, the genetic expression of MMP-3 and 7, known as catabolic factors, and production of NO and $PGE_2$ were significantly inhibited by treatment with oral administration of HFE extract. CONCLUSION: HFE extract inhibited articular cartilage degeneration through preventing extracellular matrix degradation and chondrocyte injury.

• Nutrition Research and Practice
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• 제10권6호
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• pp.569-574
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• 2016

BACKGROUND/OBJECTIVES: We investigated the anti-osteoarthritic effects of deer bone extract on the gene expressions of matrix metalloproteinases (MMPs) and collagen type II (COL2) in interleukin-$1{\beta}$-induced osteoarthritis (OA) chondrocytes. MATERIALS/METHODS: Primary rabbit chondrocytes were treated as follows: CON (PBS treatment), NC (IL-$1{\beta}$ treatment), PC (IL-$1{\beta}+100{\mu}g/mL$ glucosamine sulphate/chondroitin sulphate mixture), and DB (IL-$1{\beta}+100{\mu}g/mL$ deer bone extract). RESULTS: The results of the cell viability assay indicated that deer bone extract at doses ranging from 100 to $500{\mu}g/mL$ inhibits cell death in chondrocytes induced by IL-$1{\beta}$. Deer bone extract was able to significantly recover the mRNA expression of COL2 that was down-regulated by IL-$1{\beta}$ (NC: 0.79 vs. DB: 0.87, P < 0.05) and significantly decrease the mRNA expression of MMP-3 (NC: 2.24 vs. DB: 1.75) and -13 (NC: 1.28 vs. DB: 0.89) in OA chondrocytes (P < 0.05).CONCLUSIONS: We concluded that deer bone extract induces accumulation of COL2 through the down-regulation of MMPs in IL-$1{\beta}$-induced OA chondrocytes. Our results suggest that deer bone extract, which contains various components related to OA, including chondroitin sulphate, may possess anti-osteoarthritic properties and be of value in inhibiting the pathogenesis of OA.

• 생명과학회지
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• 제19권6호
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• pp.836-838
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• 2009

뇌졸중 치료에 사용되는 tPA는 탁월한 혈전 용해 효과를 보이고 있어 혈액의 흐름을 용이하게 하는데 중요한 역할을 한다. 그러나 tPA 치료법은 매우 짧은 시간 내에 사용해야하는 단점과 출혈, 부종과 같은 여러 가지 부작용이 수반될 수 있기 때문에 매우 제한적이다. 이전의 실험 결과에 따르면 tPA의 이러한 양면적인 현상은 MMP의 활성 조절과 관련이 있는 것으로 보고되어 있으나 세포시스템을 활용한 이들의 직접적인 효과나 조절 기전에 대한 연구는 거의 알려져 있지 않다. 본 연구는 임상에서 사용되는 tPA의 부정적인 효과를 극복하기 위한 방안을 모색하고자 tPA와 MMP 활성과의 조절 기전을 살펴보았다. 랫트의 뇌로부터 추출한 신경세포에서 tPA의 처리는 MMP의 발현을 촉진시켰고 저산소상태에서 tPA에 의한 MMP활성 증가가 더욱 가속화되었으며 JNK 신호전달 경로를 통해 조절되는 것을 확인하였다.

• Molecules and Cells
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• 제40권10호
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• pp.761-772
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• 2017

Glioblastoma is the most frequent and most aggressive brain tumor in adults. Solute carrier family 8 member 2 (SLC8A2) is only expressed in normal brain, but not present in other human normal tissues or in gliomas. Therefore, we hypothesized that SLC8A2 might be a glioma tumor suppressor gene and detected the role of SLC8A2 in glioblastoma and explored the underlying molecular mechanism. The glioblastoma U87MG cells stably transfected with the lentivirus plasmid containg SLC8A2 (U87MG-SLC8A2) and negative control (U87MG-NC) were constructed. In the present study, we found that the tumorigenicity of U87MG in nude mice was totally inhibited by SLC8A2. Overexpression of SLC8A2 had no effect on cell proliferation or cell cycle, but impaired the invasion and migration of U87MG cells, most likely through inactivating the extracellular signal-related kinases (ERK)1/2 signaling pathway, inhibiting the nuclear translocation and DNA binding activity of nuclear factor kappa B ($NF-{\kappa}B$), reducing the level of matrix metalloproteinases (MMPs) and urokinase-type plasminogen activator (uPA)-its receptor (uPAR) system (ERK1/2-$NF-{\kappa}B$-MMPs/uPA-uPAR), and altering the protein levels of epithelial to mesenchymal transitions (EMT)-associated proteins E-cardherin, vimentin and Snail. In addition, SLC8A2 inhibited the angiogenesis of U87MG cells, probably through combined inhibition of endothelium-dependent and endothelium-nondependent angiogenesis (vascular mimicry pattern). Totally, SLC8A2 serves as a tumor suppressor gene and inhibits invasion, angiogenesis and growth of glioblastoma.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1998년도 Proceedings of UNESCO-internetwork Cooperative Regional Seminar and Workshop on Bioassay Guided Isolation of Bioactive Substances from Natural Products and Microbial Products
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• pp.128-128
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• 1998

Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases that degrade extracellular matrix and basement membrane. These enzymes are play important roles in tumor cell invasion and metastasis, as well as angiogenesis and other connective tissue diseases. In our screening program for inhibitors of MMP-2 from fungal metabolites, we have isolated novel non-peptidic inhibitors of MMPs, designated gelastatin A and B from the culture broth of Westerdykella multispora F50733. The structures of gelastatin A and B were determined to be 3-(5E-hexa-2E,4E-dienylidene-2-oxo-5,6-dihydro-2H-pyran-3yl)-propanoic acid and 3-(5Z-hexa-2E,4E-dienylidene-2-oxo-5,6-dihydro-2H-pyran-3yl)-propanoic acid, respectively. Gelastatin A and B exist as a mixture of two stereoisomers in a ratio of 2: 1. The 2: 1 mixture of gelastatin A and B inhibited activated MMP-2 and MMP-9 with an IC$\sub$50/ value of 0.63, 5.29 ${\mu}$M, respectively. They inhibited the invasion of B16F10 melanoma cells through basement membrane Matrigel with dose dependent.

• Journal of Nutrition and Health
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• 제41권8호
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• pp.711-717
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• 2008

본 연구는 식물의 대표적인 색소 성분인 anthocyanin계 색소 중 cyanidin이 인체 유방암 세포 MDA-MB-231에서 세포의 이동성과 침윤성에 미치는 영향을 알아보고자 실시 되었다. 실험 결과 cyanidin의 첨가량이 증가할수록 세포의 운동성, 이동성, 침윤성이 유의적으로 억제되었다. 그러나 ECM 분해 시 암세포에서 분비되는 단백질 분해 효소인 MMP-2, MMP-9의 활성과 MMP-9의 mRNA 수준은 cyanidin에 의해 영향 받지 않는 것으로 관찰되었다. 결론적으로, cyanidin은 세포 증식에 영향을 미치지 않는 범위 내에서 암세포의 전이과정 중 이동성과 침윤성을 억제할 수 있다는 가능성이 관찰되었으나, MMPs 활성에는 영향을 미치지 않는 것으로 보아 MMPs 이외의 경로를 통해 전이 과정이 이루어지는 것으로 사료된다.