• Journal of Periodontal and Implant Science
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• 제29권3호
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• pp.677-693
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• 1999

Extracellular matrix component is degraded by enzymes of thematrix metalloproteinases(MMPs). MMPs are produced by both hemopoietic and structural cells. Increased activity of MMP-3 in periodontium is strongly associated with inflammatory periodontal disease. The purpose of the present study was to determine the effect of tetracycline analogues on the activity of MMP-3. Tetracycline-HCl, doxycycline-HCl, and minocycline-HCl were applied to huamn gingival fibroblasts at various concentrations of 10, 25, 50, 100, 200${\mu}g$/ml, and 1 hour later IL-$1{\beta}$ of 25ng/ml was added. After incubation for 24 hours the cells were reacted by enzyme-linked immunosorbent assay using proMMP-3 ELISA kit. The optical density was measured by microwell plate reader at 450nm. The relative activity of MMP-3 was calculated as the percentage of the optical density of each experimental group to that of the control. The difference of the optical density and the relative activity of MMP-3 between the experimental groups and the control wasstatistically analyzed by one way ANOVA. The results were as follows: 1. Tetracycline-HCl showed the tendency to inhibit the activity of MMP-3 at the concentration lower than 25${\mu}g$/ml, but increased significantly the activity of MMP-3 at the concentration of 200${\mu}g$/ml(p<0.05). 2. Doxycycline-HCl inhibited significantly the activity of MMP-3 at the concentration lower than 100${\mu}g$/ml, but increased significantly the activity of MMP-3 at the concentration of 200${\mu}g$/ml(p<0.05). 3. Minocycline-HCl inhibited the activity of MMP-3 at the concentration in the range of 10 to 200${\mu}g$/ml. Within the limit of the present study, the above results suggested that the low concentration of tetracycline analogues could inhibit the activity of MMP-3 induced by IL-$1{\beta}$ in human gingival fibroblasts.

• 한국수정란이식학회지
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• 제33권3호
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• pp.99-105
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• 2018

To determine the differences in the in-vitro ovum maturation process of bovine, we compared the expression of MMPs in these oocytes and cumulus cell throughout oocytes maturated. In an attempt to investigate the effect of MMP activation and inhibitors in total protein of cumulus cell and, oocytes during oocytes maturation, we examined and monitored the localization and expression of MMPs (MMP-2 and MMP-9), TIMPs (TIMP-2 and TIMP-3), as well as their expression profiles (Real-time PCR, Gelatin Zymography and ELISA). Our results that the bovine oocytes MMP-2 and MMP-9 level was significantly associated with the rate of maturity of oocytes (P<0.05). In cumulus cell, MMP-2 was highly expressed in all stages of the oocyte's maturation. The final oocytes maturation exhibited strong gelatinase activity. There was no significant correlation between cumulus cell MMP-9 and the maturation rate of oocytes. However, for the oocyte cytoplasm MMP-9 expression was significant correlation to the maturation oocytes. There was no significant correlation between cumulonimbus cells MMP-9 and oocyte maturation rates; however, for oocyte cytoplasm, MMP-9 expression was significantly correlated with mature oocyte. However, the TIMP-1 and TIMP-2 protein expression patterns are not correlated with the maturation rate of the oocyte. Our results suggest that MMP different expression pattern may regulate the morphological remodeling of oocyte's in the cumulus cell. Further, the MMP-2 expression has a strong relation with a higher maturation rate of the oocyte.

• 치위생과학회지
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• 제12권1호
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• pp.71-77
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• 2012

본 연구는 월경주기에 따른 치주조직의 변화에 관한 예비연구로, 건강한 치주조직을 가지고 있고 월경주기가 일정한 20대 여성 7명과 남성 3명을 대상으로 4주간 8회 추구조사를 하였다. 시진상 치주조직의 상태는 건강하므로 치은열구액 내 바이오마커의 변화를 기준 변수로 하여, 상악전치부 치은열구액 내 MMP-9과 MMP-8, IL-$1{\beta}$의 농도를 측정하여 비모수 검정방법으로 분석하였다. 그 결과, 1. 여성대상자에서 월경시기, 배란추정시기에 각 염증지표들이 상승하는 추세를 보였으나 변화정도는 유의하지 않았다. 2. 성별에 따른 각 염증지표들의 차이는 유의하지 않았으며, MMP-9, MMP-8의 농도는 차이가 없었으나 IL-$1{\beta}$의 농도가 남성에서 유의하게 높았다(p=0.03). 3. 검사시점별 각 염증지표들의 상관관계는 강하거나 상당한 강한 양적 선형관계를 나타내었고 배란추정 시기와 월경시기에 상관계수가 더 높게 나타났다. 4. MMP-8과 IL-$1{\beta}$의 관계는 모든 검사시점에서 유의하였으나 MMP-9의 경우, MMP-8과 IL-$1{\beta}$의 상관관계가 유의하지 않은 시점도 있었다. 따라서, 여성대상자도 월경주기에 따른 변화정도가 남성대상자와 유의한 차이가 없으므로 치주병 위험요인에 따른 치주조직 변화의 추구조사에 참여할 수 있는 근거가 마련되었다. 또한 검사지표 중에 MMP-8이 모든 시점에서 다른 지표와 유의하고 강한 상관관계를 나타내어 대표 바이오마커로 적합할 것으로 사료되었다.

• 대한화장품학회지
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• 제32권2호
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• pp.117-121
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• 2006

collagen을 분해하여 광노화 과정에 매우 중요한 역할을 하는 것으로 알려져 있는 Matrix metallo proteinases (MMP)의 활성 및 저해 인자에 대해서는 지금까지 많은 연구가 진행되어 왔지만, 녹차 카테킨의 영향에 대한 연구는 epigallocatechin-3 gallate (EGCG) 이외에는 별로 알려진 것이 없다. 본 연구에서는 카테킨이 사람 섬유아세포에서의 MMP-1의 발현과 MMP-2의 활성 및 type I procollagen 생성에 미치는 영향을 조사하였다. 또한, 녹차의 대표적인 카테킨인 EGCG를 포함하여 자연적으로 존재하는 여덟개의 카테킨을 모두 사용하여 각각의 활성을 비교하였다. 그 결과, UVA에 의해서 사람 섬유아세포에서 발현되는 MMP-1에 대해 단백질의 양적인 변화는 EGCG 및 gallocatechin-3-gallate (GCG)에서 최대 57.4, 62.8% 감소되었으며, MMP-2의 활성 역시 감소되었다. 반면에, type I procollagen에 대해서는 생성 촉진능을 보였는데, 흥미롭게도 $1{\mu}M$ 이하의 저농도에서만 효능을 나타내었다. 또한 EGCG, GCG, epicatechin-gallate (ECG) 세가지 카테킨이 0.5:1.5:1.3의 비율로 조합된 경우, procollagen 합성에 가장 높은 효과를 나타내었다. 이러한 실험 결과를 통해 녹차 카테킨은 항산화능 뿐만이 아니라 자외선에 의한 MMP의 발현과 활성을 조절함으로써 콜라겐 분해를 억제함과 동시에 콜라겐 생합성을 촉진하는 것이 가능함을 확인하였다. 따라서 녹차 카테킨은 광노화의 억제 및 피부 노화 개선에 훌륭한 천연 소재로서 응용 가능할 것으로 보인다.

• Archives of Pharmacal Research
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• 제28권11호
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• pp.1257-1262
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• 2005

MMP-9 is a metalloproteinase capable of basement membrane degradation in vivo. Expression of MMP-9 can be found in normal conditions such as trophoblasts, osteoclasts, and leukocytes and their precursors. They also occur as well as in pathological conditions, such as the invasive growth of primary tumors, metastasis, angiogenesis, rheumatoid arthritis, and periodontal diseases. MMP-9 upregulation can be highly induced by a wide range of agents. These agents include growth factors, cytokines, cell-cell, and cell-ECM adhesion molecules, and agents altering cell shape. Here, we observed that TNF-$\alpha$ stimulated human monocytic cell line, HL-60 produced MMP-9 in a dose and time dependent manner. Real time PCR results indicated transcriptional upregulation of MMP-9 as early as 3 h post TNF-$\alpha$ stimulation. To investigate the signaling pathway underlined in TNF-$\alpha$ induced MMP-9 expression, three MAP kinase inhibitors were added to cells 1 h prior to TNF-$\alpha$ treatment. The ERK inhibitor completely abolished MMP-9 expression by TNF-$\alpha$. But neither p38 MAP kinase nor JNK inhibitor had an effect on TNF-$\alpha$ induced MMP-9 expression, suggesting that ERK activation is required for the MMP-9 induction by TNF-$\alpha$. Taken together, we found that TNF-$\alpha$ stimulation facilitates ERK activation, which results in the transcriptional upregulation of MMP-9 gene and subsequent MMP-9 production and secretion.

• Natural Product Sciences
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• 제27권3호
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• pp.151-160
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• 2021

Under some pathological conditions such as osteoarthritis, matrix metalloproteinases (MMPs) including MMP-13 have an important role in degrading cartilage materials. When the regulatory effects of some herbal extracts on MMP-13 expression were examined to evaluate the cartilage-protective potential, the ethanol extract of the radix of Viscum album was found to strongly downregulate MMP-13 induction in IL-1β-treated chondrocytes, SW1353 cells. Based on this finding, activity-guided separation was carried out, which yielded five constituents identified as 3,5-dihydroxy-1,7-bis(4-hydroxyphenyl)heptane (1), hesperetin-7-glucoside (2), syringin (3), homoflavoyadorinin B (4), and 4,4'-dihydroxy-3,6'-dimethoxychalcone-2'-glucoside (5). Of these, 1 and 5 significantly inhibited MMP-13 expression in SW1353 cells, with 5 being the most potent. Compound 5, a chalcone derivative, showed the downregulation of MMP-13 at 20 - 100 μM. The mechanism study revealed that 5 exerted MMP-13 down-regulatory action, at least in part, by interrupting the signal transducer and activator of transcription 1 (STAT1) activation pathway. Furthermore, this compound protected against cartilage degradation in an IL-1-treated rabbit cartilage explant culture. All these findings demonstrated for the first time that Viscum album and its constituents, especially chalcone derivative (5), possessed cartilage-protective activity. These natural products may have the potential for alleviating cartilage degradation.

• 한국식품영양학회지
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• 제25권4호
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• pp.713-718
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• 2012

향나무 에탄올 추출물에 대한 암 전이 억제 효과를 측정하기 위하여 세포 수준에서 암 전이에 밀접히 관련되어 있는 galectin-3에 대한 억제 효과를 colon 26-M3.1 lung carcinoma에서 측정하였다. 향나무 추출물 $5{\mu}g/m{\ell}$, $50{\mu}g/m{\ell}$ 및 $500{\mu}g/m{\ell}$ 처리 시, 농도 의존적으로 galectin-3에 대한 저해 효과를 나타내었다. 한편, 암 전이 관련 있는 또 다른 단백질로 MMP 효소에 대한 직접적인 억제효과를 측정한 결과, 향나무 추출물 $5{\mu}g/m{\ell}$, $50{\mu}g/m{\ell}$ 및 $500{\mu}g/m{\ell}$ 처리 시 직접적으로 MMP-1, MMP-2 및 MMP-9 효소에 대해서 농도의존적인 저해 효과는 나타났으나, 강한 활성으로 평가되지는 못하였다. Colon 26-M3.1 lung carcinoma을 이용한 in vivo mouse 모델에서 향나무 추출은 농도 의존적으로 전이 억제 효과를 나타내었고, MMP-2 활성화 물질인 relaxin과 병용투여 시, relaxin의 기능에 영향을 받지 않는 것으로 나타났다. 따라서 in vivo mouse 모델에서 나타난 암 전이 억제 효과는 galectin-3 저해로 인한 효과로 사료된다.

• 한국식물생명공학회:학술대회논문집
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• 한국식물생명공학회 2004년도 생명공학 실용화를 위한 비젼
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• pp.81-90
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• 2004

Sialic acid containing glycosphingolipids (gangliosides) have been implicated in the regulation of various biological phenomena such as atherosclerosis. Recent report suggeststhat exogenously supplied disialoganglioside (GD3) serves a dual role in vascular smooth muscle cells (VSMC) proliferation and apoptosis. However, the role of the GD3 synthase gene in VSMC responses has not yet been elucidated. To determine whether a ganglioside is able to modulate VSMC growth. the effect of overexpression of the GD3 synthase gene on DNA synthesis was examined. The results show that the overexpression of this gene has a potent inhibitory effect on DNA synthesis and ERK phosphorylation in cultured VSMC in the presence of PDGF. The suppression of the GD3 synthase gene was correlated with the down-regulation of cyclinE/CDK2. the up-regulation of the CDK inhibitor p21 and blocking of the p27 inhibition,whereas up-regulation of p53 as the result of GD3 synthase gene expression was not observed. Consistently, blockade of GD3 function with anti-GD3 antibody reversed VSMC proliferation and cell cycle proteins. The expression of the CD3 synthase gene also led to the inhibition of TNF--induced matrix metalloproteinase-9 (MMP-9) expression in VSMC as determined by zymography and immunoblot. Furthermore, GD3 synthase gene expression strongly decreased MMP-9 promoteractivlty in response to TNF-. This inhibition was characterized by the down-regulation of MMP-9,which was Iranscriptionally regulated at NF-B and activation protein-1 (AP-1) sites in the MMP-9promoter Finally, the overexpression of MMP-9 in GD3 synthase transfectant cells rescued VSMC proliferation. However MMP-2 overexpression was not affected the cell proliferation. These findings suggest that the fl13 synthase gene represents a physiological modulator of VSMC responses that may contribute to plaque instability in atherosclerosis.

• Nutrition Research and Practice
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• 제15권4호
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• pp.444-455
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• 2021

BACKGROUND/OBJECTIVES: Adipocytes undergo angiogenesis to receive nutrients and oxygen needed for adipocyte' growth and differentiation. No study relating quercetin with angiogenesis in adipocytes exists. Therefore, this study investigated the role of quercetin on adipogenesis in 3T3-L1 cells, acting through matrix metalloproteinases (MMPs). MATERIALS/METHODS: After proliferating preadipocytes into adipocytes, various quercetin concentrations were added to adipocytes, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were performed to evaluate cell proliferation. Glycerol-3-phosphate dehydrogenase (GPDH) activity was investigated as an indicator of fat accumulation. The mRNA expressions of transcription factors related to adipocyte differentiation, CCAAT/enhancer-binding proteins (C/EBPs), peroxisomal proliferatoractivated receptors (PPAR)-γ, and adipocyte protein 2 (aP2), were investigated. The mRNA expressions of proteins related to angiogenesis, vascular endothelial growth factor (VEGF)-α, vascular endothelial growth factor receptor (VEGFR)-2, MMP-2, and MMP-9, were investigated. Enzyme activities and concentrations of MMP-2 and MMP-9 were also measured. RESULTS: Quercetin treatment suppressed fat accumulation and the expressions of adipocyte differentiation-related genes (C/EBPα, C/EBPβ, PPAR-γ, and aP2) in a concentration-dependent manner in 3T3-L1 cells. Quercetin treatments reduced the mRNA expressions of VEGF-α, VEGFR-2, MMP-2, and MMP-9 in 3T3-L1 cells. The activities and concentrations of MMP-2 and MMP-9 were also decreased significantly as the concentration of quercetin increased. CONCLUSIONS: The results confirm that quercetin inhibits adipose tissue differentiation and fat accumulation in 3T3-L1 cells, which could occur through inhibition of the angiogenesis process related to MMPs.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제32권4호
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• pp.352-359
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• 2006

MMP-2 and MMP-9, type IV collagenases which degrade basement membrane, have been known to play important roles in invasion and metastasis of tumor cells, In addition, they seem to be involved in cell differentiation, apoptosis, angiogenesis and immunity, etc. We immunohistochemically examined epithelial and stromal expressions of MMP-2 and MMP-9 in irritation fibroma, oral leukoplakia, and oral squamous cell carcinoma (OSCC) and have some results as follows: 1. Irritation fibromas, oral leukoplakias and OSCCs mostly showed increased expression of MMP-2 and MMP-9 in the epithelium and connective tissue compared with normal mucosa. 2. There was a significant difference in the epithelial expression of MMP-2 and MMP-9 between irritation fibroma and oral leukoplakia. 3. There was a significant difference in the epithelial and stromal expression of MMP-2 and MMP-9 between irritation fibroma and OSCC. 4. There was a significant difference in the stromal expression of MMP-9 between oral leukoplakia and OSCC. We concluded that rritation fibroma, oral leukoplakia and OSCC have somewhat different characteristics of MMP-2 and MMP-9 expressions, which perhaps result from different pathogenesis.