[논문]치주염 환자의 치은열구액에서 MMPs와 TIMPs의 양의 변화

이선윤; 정연호; 김경화; 양병근; 한수부; 정종평; 김태일; 구영; 이용무; 고재승; 류인철

doi:10.5051/jkape.2004.34.1.139

[국내논문] 치주염 환자의 치은열구액에서 MMPs와 TIMPs의 양의 변화
Matrix metalloproteinases and Tissue inhibitors of matrix metalloproteinases in gingival crevicular fluids of periodontitis patients 원문보기

대한치주과학회지 = The journal of Korean academy of periodontology, v.34 no.1, 2004년, pp.139 - 148

초록
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MMPs(Matrix metalloproteinases)는 치주질환에서 주된 조직파괴단백분해효소인 것은 알려져 있고 TIMPs(Tissue inhibitor of Matrix metalloproteinase)는 MMPs의 작용을 억제한다라고 알려져 있다. 이 둘간의 불균형으로 인해서 조직파괴가 더 가속화될 수 있다. 이 두 연구의 목적은 ELISA kit를 사용하여 특정 MMPs(1,2,3,8,9,13)과 TIMPs(1,2)의 양이 건강한 환자와 비교하여서 치주염 환자에서 달라지는지 알아보고 MMPs(1,2,3,8,9,13), TIMPs(1,2)와 치은열구깊이와 GI score와의 관계를 알아보기로 한다. 8명의 만성 치주염 환자와 4명의 급속진행형 치주염 환자가 실험군으로 참여하였고 5명의 건강한 치주조직을 환자가 대조군으로 참여하였다. 임상적인 측정은 GI score와 치주낭측정을 통하여 이루어졌다. 8명의 만성 치주염을 가진 환자와 4명의 급속진행형 치주염을 가진 환자에서 각각 치주낭 깊이가 3mm이하인 부위에서 6개의 치은열구액 표본과 치주낭 깊이가 6mm 이상인 곳에서 6개의 치은열구액 표본을 채취하였다. 건강한 치주조직을 가진 5명의 환자는 단지 치주낭깊이가 3mm 이하인 건강한 부위에서만 치은열구액 표본을 제공하였다. MMPs(1,2,3,8,9,13)과 MIMPs(1,2)의 측정은 Human Biotrack ELISA kit를 사용하여서 측정하였다. 통계처리는 MMPs, MIMPs의 실험군과 대조군의 차이는 Kruskal-Wallis test를 사용하였고 MMPs, TIMPs와 치주낭 깊이와 GI score의 관계정도는 Pearson's correlation coefficient를 사용하였다. 실험결과 대조군과 비교하여 만성 치주염 환자에서 치주낭 깊이가 6mm 이상인 부위에서 MMP9의 수치가 통계적으로 유의할만하게 높았으며(p=0.04) MIMP2의 수치가 대조군과 비교하여 치주낭 깊이가 3mm 이하인 부위를 가진 만성치주염 환자에서 통계적으로 유의할만하게 높았다(=0.049). MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 치주낭 깊이의 관계에서 둘간의 통계적으로 유의할만한 관계는 존재하지 않았으나 MMP1(r=0.35)과 MMP2(r=0.31)가 상대적으로 높은 관계를 보였다. 또한 MMPs(1,2,3,8,9,13), MIMPs(1,2)의 활동성과 GI score의 관계에서도 둘간의 통계학적으로 유의할만한 관계는 존재하지 않으나 MMP1(r=0.4), MMP2(r=0.29), MMP9(r=0.26)가 상대적으로 높은 관계를 보였다. 이 실험의 결과로 볼 때 MMP9가 만성치주염 환자의 질환이 있는 부위에서만 염증의 지표가 될 수 있으며 MIMP2가 만성치주염 환자의 염증이 없는 부위에서 높은 농도로 존재하는 것으로 보아서 MIMP2가 MMPs에 대한 억제작용을 하여서 염증의 진행을 방해하는 역할을 한다라고 볼 수 있다.

주제어

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제안 방법

The purpose of this study is to determine whether specific MMPs(-l, -2-3, -8-9, -13) andHMPs(-l, -2) are present more in GCF of periodontitis patients than in that of healthy patients by using ELISA assays, and whether the results of these assays have relationship with periodontal probing depth and GI scores, which are the most useful methods in evaluating periodontal status and identify the degrees of periodontal disease in periodontititis patients.

대상 데이터

Eight chronic periodontitis patients and 4 aggresiive periodontitis patients with moderate to advanced periodontitis, who have more than 14 remaining teeth except the 3rd molar, 5-6 teeth whose probing pocket depth >6mm and definite moderate to advanced periodontitis in radiograph were selected for test group. And 5 patients with clinically healthy periodontal status who have no pocket depth exceeding 5mm were selected for control group.
Patients for this study were selected from the departments of periodontology , Seoul National University Dental Hospital.
Six GCF samples from healthy(PD 6mm) were collected respectively from 8 patients with chronic periodontitis and 4 patients with aggressive periodontitis.

데이터처리

Because the sample size of each group was not enough to perform ANOVA, Kruskal-wallis test was used. Whether there was difference in MMPs and TIMPs levels between at least 2 groups or not.
Table 4. Pearson correlation coefficient of MMPs and TIMPs with PD of each group. 0 is p-value for no correlation
To analyze the relationship between pocket depth and assays of MMPs(-l, -2, -3, -8, -9, -13) and TIMPs(-l, -2), Pearson correlation analysis was used was used to analyze the relationship between GI score and assays of MMPs and TIMPs.

성능/효과

And also there was statistically significant difference in TIMP-2 level between chronic periodontitis patients (PD 6mm site) compared to healthy patients.
As reviewed, Whether TIMP level is higher or lower in inflamed site than in healthy site is still controvertial and different GCF sampling methods might result in conflicting results.
Assessment of subjects from each of the four groups(control, gingivitis, chronic periodontitis, localized juvenile periodontitis) revealed that more collagenolytic activity was present in GCF from gingivitis patients than from controls and that still more was present than in GCF from periodontitis patients than from those with gingivitis. No difference was observed between the two periodontitis groups (Villela B 1987).
In conclusion, only MMP-9 could be a possible marker in pocket depth >6mm site in chronic periodontitis patients and TIMP-2 could be a marker in pocket depth <3mm of chronic periodontitis patients.
In this study, when data from different groups were pooled, comparing the relationship between activities of MMPs(-l, -2, -3, -8, -9, -13), TIMPs(-l -2) and PD, there is no statistically significant correlationship but MMP-1 (r=0.35) and MMP-2(r=0.31) had relatively high correlationships. When data from different groups were separately analyzed, there is no statistically significant correlationship.
The result from this study is that assessment of subjects from 4 groups revealed that higher MMP-9 activity was found in deep pocket(>6mm) sites of chronic periodontitis patients than control group. The observation that the lev시 of MMP-9 was elevated in inflamed sites of chronoic periodontitis patients suggests that MMP-9 could be a marker of inflammation in chronic periodontitis patients.
The results of Ingman, Makela and Anne-Laure are coincident with our results in that the level of MMP-9 in inflamed site of chronic periodontitis patients is higher than control group.
1-3. The results showed that there was a statistically significant difference in MMP-9 level between chronic periodontitis patients(PD > 6mm site) and healthy patients(Table 2-1, Table 2-2). And also there was statistically significant difference in TIMP-2 level between chronic periodontitis patients (PD < 3mm site) and healthy patients(Table 2-1, 2-2), Elevated level of MMP-9 was found in chronic periodontitis patients(PD > 6mm site) compared to healthy patients.
Thus, pocket depth could not reflect amounts of MMPs and TIMPs in GCF. When data from different groups were pooled, comparing the relationship between activities of MMPs(-l, -2, -3, -8, -9, -13), TIMPs(-l, -2), and GI score showed that there is statistically significant positive correlationship between MMP-1 and GI score(p-value=0.03). MMP-l(r=0.
When data from different groups were pooled, comparing the relationship between amounts of MMPs(-l, -2, -3, -8, -9, -13), TIMPs(-l, -2) and GI score showed that there was statistically significant positive correlationship between MMP-1 and GI score(p-value=0.03)(see Table 5). And relatively high correlationship was found in MMP-l(r=0.

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