• Title/Summary/Keyword: Matrix metalloproteinase-2

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Correlation of expression and activity of matrix metalloproteinase-9 and -2 in human gingival cells of periodontitis patients

  • Kim, Kyung-A;Chung, Soo-Bong;Hawng, Eun-Young;Noh, Seung-Hyun;Song, Kwon-Ho;Kim, Hanna-Hyun;Kim, Cheorl-Ho;Park, Young-Guk
    • Journal of Periodontal and Implant Science
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    • v.43 no.1
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    • pp.24-29
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    • 2013
  • Purpose: Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, and they are inducible enzymes depending on an inflammatory environment such as periodontitis and bacterial infection in periodontal tissue. Gingival inflammation has been postulated to be correlated with the production of MMP-2 and MMP-9. The objective of this study was to quantify the expression and activity of MMP-9 and -2, and to determine the correlation between activity and expression of these MMPs in human gingival tissues with periodontitis. Methods: The gingival tissues of 13 patients were homogenized in $500{\mu}L$ of phosphate buffered saline with a protease inhibitor cocktail. The expression and activity of MMP-2 and -9 were measured by enzyme-linked immunosorbent assay and Western blot analysis, and quantified by a densitometer. For the correlation line, statistical analysis was performed using the Systat software package. Results: MMP-9 was highly expressed in all gingival tissue samples, whereas MMP-2 was underexpressed compared with MMP-9. MMP-9 activity increased together with the MMP-9 expression level, with a positive correlation (r=0.793, P=0.01). The correlation was not observed in MMP-2. Conclusions: The expression of MMP-2 and -9 might contribute to periodontal physiological and pathological processes, and the degree of MMP-9 expression and activity are predictive indicators relevant to the progression of periodontitis.

ROLE OF NF${\kappa}B$ IN TOLL-LIKE RECEPTOR 9-MEDIATED MATRIX METALLOPROTEINASE-9 EXPRESSION (Toll-like receptor 9-매개에 의한 matrix metalloproteinase-9 발현에서 NF${\kappa}B$의 역할)

  • Lee, Sang-Hoon;Chin, Byung-Rho;Baek, Suk-Hwan
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.33 no.6
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    • pp.636-642
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    • 2007
  • Background: CpG DNA plays an important role in immune cell function. This study examined whether the temporal control of toll-like receptor (TLR)9 by CpG DNA can regulate the expression of matrix metalloproteinase-9(MMP-9). Methods and materials: Macrophages were cultured in the presence of 10% FBS. For the various MMP genes analysis, RT-PCR and real-time PCR were performed. In addition, zymography assay performed for the MMP activity. The phosphorylation assay did for the ERK1/2 and NF${\kappa}B$ activation, and luciferase promoter assay was for the NF${\kappa}B$ activity. Results: CpG DNA induced the mRNA expression of MMP-2, MMP-9, and MMP-13, but not of MMP-7, MMP-8, and MMP-12, in a time-dependent manner. Especially, the mRNA expression of MMP-9 was strongly induced by CpG DNA using real-time RT-PCR. The TLR9 inhibitor, chloroquine, suppressed CpG DNA-induced MMP-9 expression and its activity. Moreover, CpG DNA induced the phosphorylation of ERK and the inhibition of ERK by U0126 suppressed CpG DNA-induced MMP-9 expression and its activity. CpG DNA stimulated $I{\kappa}B-{\alpha}$ degradation and luciferase activity. In addition, pretreatment of SN-50, the inhibitor of NF${\kappa}B$, strongly blocked the CpG DNA-induced MMP-9 expression and activity. Conclusion: These observations suggest that CpG DNA may play important roles in the activation of macrophages by regulating the production of MMP-9 via the sequential TLR9-ERK-NF${\kappa}B$ signaling pathway.

Inhibition of Migration and Invasion of LNCap Human Prostate Carcinoma Cells by Doxorubicin through Inhibition of Matrix Metalloproteinase Activity and Tightening of Tight Junctions (Doxorubicin에 의한 치밀결합 강화 및 MMPs의 활성 억제를 통한 LNCap 전립선 암세포의 이동성 및 침윤성의 억제)

  • Choi, Yung Hyun;Shin, Dong Yeok;Kim, Wun-Jae
    • Journal of Life Science
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    • v.24 no.6
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    • pp.700-706
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    • 2014
  • Doxorubicin (trade name adriamycin), an anthracycline antibiotic, is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, and soft tissue sarcomas. It is closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA. Its most serious adverse effect is life-threatening heart damage. Its anti-metastatic mechanisms in human prostate carcinomas are not fully understood. In this study, we used LNCap human prostate carcinoma cells to investigate the inhibitory effects of doxorubicin on cell motility and invasion, two critical cellular processes that are often deregulated during metastasis. Doxorubicin treatment inhibited cell migration and invasiveness of LNCap cells without showing any toxicity. Doxorubicin treatment also suppressed the activity and expression of matrix metalloproteinase (MMP)-2 and MMP-9, which were associated with up-regulated expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 in LNCap cells. Doxorubicin treatment also attenuated the expression levels of claudin family members (claudin-1, -2,-3 and -4), major components of tightening of tight junctions (TJs) and increased the tightening of TJs, as demonstrated by an increase in transepithelial electrical resistance. The present findings demonstrate that doxorubicin reduces the migration and invasion of prostate carcinomas LNCap cells by modulating the activity of TJs and MMPs.

Preparation of Camel Milk Liposome and Its Anti-Aging Effects (낙타유가 함유된 리포좀 제조 및 피부 노화 개선 효과 연구)

  • Choi, Sung Kyu;Park, Kun Dong;Kim, Da Ae;Lee, Dae Woo;Kim, Yun Jeong
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.40 no.2
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    • pp.155-162
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    • 2014
  • In this study, in order to know the application for cosmetic ingredient, the liposome contained camel milk was prepared and tested in human skin fibroblast. Collagen and hyaluronan synthase-3 (HAS-3) gene expression were increased by camel milk liposome in a concentration-dependent manner, whereas elastase activity and matrix metalloproteinase (MMP)-1 gene expression were inhibited. We also found that camel milk liposome regenerated UVB-damaged fibroblast. As the results, we suggest that the liposome contained camel milk is applicable for a potential cosmetic ingredient to improve anti-aging effect.

Inhibitory Effects of (-)Epigallocatechin Gallate and Quercetin on Phorbol 12-Myristate 13-Acetate-Induced Secretion of Metalloproteinase-2 and Metalloproteinase-9

  • Kang Sang-Wook;Choi Yean-Jung;Choi Jung-Suk;Kwon Hyang-Mi;Bae Ji-Young;Park Eun-Hee;Ji Geun-Eog;Kang Il-Jun;Kang Young-Hee
    • Nutritional Sciences
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    • v.9 no.3
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    • pp.145-151
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    • 2006
  • Matrix metalloproteinases (MMP) play an important role in the extracellular matrix (ECM) degradation undetphysiological and pathological conditions. The present study examined the influence of (-)epigallocatechin gallate and quercetin on phorbol-12-myristate 13-acetate (PMA)-induced secretion of MMP-2 and MMP-9, when human umbilical vein endothelial cells (HUVEC) were treated with (-)epigallocatechin gallate and quercetin at supraphysiological concentrations of $25{\mu}mol/L$. No cytotoxicity was observed by MIT assay in response to a treatment with PMA in the presence of (-)epigallocatechin gallate and quercetin. Western blot analysis and gelatin zymography revealed that exposure of HUVEC to PMA enhanced the levels and gelatinolytic activities of pro and active forms of MMP-2 and active form of MMP-9. (-)Epigallocatechin gallate attenuated PMA-stimulated secretion of active forms of MMP-2 and MMP-9 concomitantly with a loss of activities of these enzymes, which was related to the decreased mRNA levels of MMP. Quercetin was more potent than (-)epigallocatechin gallate in alleviating MMP-9 protein secretion and activity with a decrease in MMP-9 mRNA accumulation. Taken together, the results indicated that (-)epigallocatechin gallte and quercetin exhibited inhibitory effects on MMP activity and may qualify as chemopreventive and cardiovascular protective agents.

Matrix Metalloproteinase-3 Gene Polymorphisms (A(-267)G, A658G, T813C) is Associated with Type 2 Diabetes in Koreans (제2형 당뇨병과 MMP3 (A(-267)G, A658G, T813C)의 다형성과의 연관성)

  • Yoo, Min;Kim, Hyo-Jeong;Qing, Ye;Kim, Jong-Won;Kim, Su-Won
    • Journal of Life Science
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    • v.20 no.4
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    • pp.602-606
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    • 2010
  • Type 2 diabetes is a typical polygenic disease complex, for which several common risk alleles have been identified. Proteins in the matrix metalloproteinase-3 (MMP3) family are involved in the breakdown of the extracellular matrix in normal physiological processes such as embryonic development, reproduction and tissue remodeling, as well as in disease processes. Therefore, we investigated the genotype for the A(-267)G, A658G and T813C polymorphisms in the MMP3 gene in the Korean population and compared genotypes of patients with those of the control group. 200 patients (male 108, female 92), who had previously been diagnosed with type 2 diabetes (T2DM) and 100 control subjects (male 36, female 64) participated in this study. There was a strong association between A(-267)G and A658G polymorphism in the MMP3 gene and T2DM. The present study shows that MMP3 polymorphisms (A(-267)G and A658G) may be associated with the pathogenesis of T2DM. Further studies with a larger population may be needed for the development of diagnostic methods at a genetic level, such as DNA chip.

Changes in Matrix Metalloproteinase and Tissue Inhibitors of Metalloproteinase in Patients with Rotator Cuff Tears

  • Kwon, Oh-Soo;Kim, Young-Yul;Ha, Ji Yoon;Kang, Han Bit
    • Clinics in Shoulder and Elbow
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    • v.17 no.2
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    • pp.64-67
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    • 2014
  • Background: The purpose of this study was to determine whether in patients with rotator cuff tears a correlation exists between molecular changes and clinical parameters such as age, duration of symptom, range of motion, and tear size. Molecular changes of matrix metalloproteinase (MMP) and tissue inhibitor of metalloproteinase (TIMP) were assessed by measuring messenger RNA (mRNA) levels of the two proteins. Methods: The rotator cuff tissue from was obtained from the edge of a torn tendon revealed after debridement by a motorized shaver. Using the sample of rotator cuff tissue, the reverse transcription polymerase chain reaction was performed to quantify MMP-2 and TIMP-2 mRNA expression. To determine whether mRNA levels and the clinical variables, such as age, defect size, range of motion (ROM) of shoulder, and duration of symptoms, show any correlation, Spearman's correlation coefficients were used to test for significant differences. Results: There was an inverse correlation between the mRNA levels of MMP-2 and TIMP-2 from the torn rotator cuff tendons regardless of the clinical variables. However, comparison of mRNA levels versus clinical parameters such as age, defect size, range of motion and duration of symptoms revealed a number of findings. We found a significant correlation between age and mRNA levels of MMP-2 from torn cuffs (r = 0.513, p = 0.021). Further, we found a significant correlation between defect size in the full thickness tears and mRNA levels of MMP-2 (r = 0.454, p = 0.045). Conversely, no significant association between mRNA levels of MMP-2 and ROM or duration of symptom was found. Conclusions: Our results suggest that both MMP-2 and TIMP-2 may be involved in the disease process of rotator cuff tears. Although the level of mRNA expression of MMP-2 and TMP-2 remain constant in torn rotator cuffs irrespective of the clinical variables, their levels may be influenced by age and defect size, which could account to change in tendon degradation and the healing process.

Serum Level of Matrix Metalloproteinase-2 and -9 in Patients with Laryngeal Squamous Cell Carcinoma and Clinical Significance

  • Lotfi, Alireza;Mohammadi, Ghodrat;Saniee, Lale;Mousaviagdas, Mehrnoosh;Chavoshi, Hadi;Tavassoli, Atena
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.15
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    • pp.6749-6751
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    • 2015
  • Background: Laryngeal cancer is an important malignancy in head and neck area and squamous cell carcinoma (SCC) is the most common type accounting for 95% of cases. Increase in matrix metalloproteinases (MMPs) in different tumors and their correlation with tumor invasiveness has been documented. However, most studies have evaluated MMP-2 and MMP-9 expression and few have evaluated serum levels. The aim of current study was to evaluate serum levels in patients with laryngeal SCC compared to normal subjects and assess any relation with tumor clinicopathological findings. Materials and Methods: In this case control study, 20 patients with oral SCC and 20 healthy subjects were included. Serum levels of MMP-2 and MMP-9 were compared between groups and correlations with findings including grade (T) and node involvement (N) were evaluated. Results: Patients with laryngeal SCC had significantly higher serum levels of MMP-2 (p=0.01) and MMP-9 (p=0.03) compared to healthy subjects. Patients with higher T stage (T3,4) had significantly higher MMP-2 (p=0.04) and MMP-9 (p=0.01). There was significant positive correlation between serum levels of MMP-2 with T stage (r=0.45, p=0.04) and lymph node involvement (r=0.563, p=0.01) and between levels of MMP-9 with T stage (r=0.527, p=0.01). Conclusions: Our results showed that compared to healthy subjects, both MMP-2 and MMP-9 are significantly increased in serum of laryngeal SCC cases. MMP-2 was correlated with lymph node involvement while MMP-9 has stronger correlation with T stage compared to MMP-2.

BONE REGENERATION WITH MMP SENSITIVE HYALURONIC ACID-BASED HYDROGEL, rhBMP-2 AND NANOPARTICLES IN RAT CALVARIAL CRITICAL SIZE DEFECT(CSD) MODEL (Matrix metalloproteinase(MMP) sensitive hyaluronic acid hydrogel-nanoparticle complex와 rhBMP-2를 이용한 골재생)

  • Nam, Jeong-Hun;Park, Jong-Chul;Yu, Sang-Bae;Chung, Yong-Il;Tae, Gi-Yoong;Kim, Jung-Ju;Park, Yong-Doo;Jahng, Jeong-Won;Lee, Jong-Ho
    • Journal of the Korean Association of Oral and Maxillofacial Surgeons
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    • v.35 no.3
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    • pp.137-145
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    • 2009
  • As an efficient controlled release system for rhBMP-2, a functional nanoparticle-hydrogel complex, incorporated with matrix metalloproteinase(MMP) sensitive peptide cross-linker, was developed and used as a bone transplant. In vivo bone formation was evaluated by soft x-ray, histology, alkaline phosphatase(ALP) activity and mineral contents analysis, based on the rat calvarial critical size defect(8mm in diameter) model. Significantly, effective bone regeneration was achieved with the rhBMP-2 loaded MMP sensitive hyaluronic acid(HA) based hydrogel-Nanoparticles(NP) complex, as compared to only MMP HA, the MMP HA-NP without rhBMP-2, or even with the rhBMP-2. These improvements included the formation pattern of bone and functional marrow, the degree of calcium quantification, and the ALP activity. These results indicate that the MMP sensitive HA with nano-particle complex can be a promising candidate for a new bone defect replacement matrix, and an enhanced rhBMP-2 scaffold.