{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1363670318982448896.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1902/jop.2000.71.7.1158"}},{"identifier":{"@type":"URI","@value":"https://aap.onlinelibrary.wiley.com/doi/pdf/10.1902/jop.2000.71.7.1158"}},{"identifier":{"@type":"PMID","@value":"10960024"}},{"identifier":{"@type":"NAID","@value":"30015371801"}}],"dc:title":[{"@value":"Effects of Bisphosphonate on Matrix Metalloproteinase Enzymes in Human Periodontal Ligament Cells"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p><jats:bold>Background:</jats:bold> The host response is a critical component in the pathogenesis of periodontitis. In fact, the clinical benefits associated with regulating the host response have been demonstrated in studies using several different classes of drugs. Biophosphates are one host‐modulating class of drugs that has demonstrated this ability. These drugs are clinically effective at reducing bone resorption and have shown the ability to inhibit host degradative enzymes, specifically the matrix metalloproteinases (MMPs). Therefore, the purpose of this study was to investigate the regulatory effects of a bisphosphonate, tiludronate, on MMP levels and activity in human periodontal cells.</jats:p><jats:p><jats:bold>Methods:</jats:bold> MMP‐1 and MMP‐3 were assessed in cultured human periodontal ligament cells treated with a bisphosphonate, tiludronate. Reverse transcription‐polymerase chain reaction was used to identify mRNA levels for both enzymes, and also for tissue inhibitors (TIMP‐1). Enzyme immunoassay (EIA) and immunocytochemistry were used to assess MMP proteins in these cell cultures. Enzyme activity was assessed using FITCconjugated substrates and quantitated using spectrophotofluorometry.</jats:p><jats:p><jats:bold>Results:</jats:bold> Tiludronate significantly inhibited both MMP‐1 and MMP‐3 activity in a concentration‐dependent manner. A maximal reduction in activity of 35% was achieved for each of the enzymes at a 10<jats:sup>‐4</jats:sup> M concentration. Tiludronate did not have a significant effect on the mRNA levels for MMP‐1, MMP‐3, or TIMP‐1. Similarly, there were no effects noted for either MMP‐1 or MMP‐3 on the protein level.</jats:p><jats:p><jats:bold>Conclusions:</jats:bold> This study demonstrates an inhibitory effect of tiludronate on the activity of both MMP‐1 and MMP‐3. These effects appear to occur without altering either mRNA or protein levels for these enzymes, supporting a possible mechanism of action that involves the ability of bisphosphonates to chelate cations from the MMPs. Furthermore, these results support the continued investigation of these drugs as potential therapeutic agents in periodontal disease. <jats:italic>J Periodontol 2000;71:1158‐1166.</jats:italic></jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1583387448844156672","@type":"Researcher","foaf:name":[{"@value":"H. Nakaya"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318982448899","@type":"Researcher","foaf:name":[{"@value":"G. Osawa"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318982448897","@type":"Researcher","foaf:name":[{"@value":"N. Iwasaki"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318982448900","@type":"Researcher","foaf:name":[{"@value":"D.L. Cochran"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318982448896","@type":"Researcher","foaf:name":[{"@value":"K. Kamoi"}]},{"@id":"https://cir.nii.ac.jp/crid/1383670318982448901","@type":"Researcher","foaf:name":[{"@value":"T.W. Oates"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"00223492"},{"@type":"EISSN","@value":"19433670"}],"prism:publicationName":[{"@value":"Journal of Periodontology"}],"dc:publisher":[{"@value":"Wiley"}],"prism:publicationDate":"2000-07","prism:volume":"71","prism:number":"7","prism:startingPage":"1158","prism:endingPage":"1166"},"reviewed":"false","dc:rights":["http://onlinelibrary.wiley.com/termsAndConditions#vor"],"url":[{"@id":"https://aap.onlinelibrary.wiley.com/doi/pdf/10.1902/jop.2000.71.7.1158"}],"createdAt":"2005-02-02","modifiedAt":"2025-10-19","foaf:topic":[{"@id":"https://cir.nii.ac.jp/all?q=Analysis%20of%20Variance","dc:title":"Analysis of Variance"},{"@id":"https://cir.nii.ac.jp/all?q=Tissue%20Inhibitor%20of%20Metalloproteinase-1","dc:title":"Tissue Inhibitor of Metalloproteinase-1"},{"@id":"https://cir.nii.ac.jp/all?q=Diphosphonates","dc:title":"Diphosphonates"},{"@id":"https://cir.nii.ac.jp/all?q=Dose-Response%20Relationship,%20Drug","dc:title":"Dose-Response Relationship, Drug"},{"@id":"https://cir.nii.ac.jp/all?q=Molecular%20Structure","dc:title":"Molecular Structure"},{"@id":"https://cir.nii.ac.jp/all?q=Periodontal%20Ligament","dc:title":"Periodontal Ligament"},{"@id":"https://cir.nii.ac.jp/all?q=Reverse%20Transcriptase%20Polymerase%20Chain%20Reaction","dc:title":"Reverse Transcriptase Polymerase Chain Reaction"},{"@id":"https://cir.nii.ac.jp/all?q=Matrix%20Metalloproteinase%20Inhibitors","dc:title":"Matrix Metalloproteinase Inhibitors"},{"@id":"https://cir.nii.ac.jp/all?q=Immunohistochemistry","dc:title":"Immunohistochemistry"},{"@id":"https://cir.nii.ac.jp/all?q=Up-Regulation","dc:title":"Up-Regulation"},{"@id":"https://cir.nii.ac.jp/all?q=Humans","dc:title":"Humans"},{"@id":"https://cir.nii.ac.jp/all?q=RNA,%20Messenger","dc:title":"RNA, Messenger"},{"@id":"https://cir.nii.ac.jp/all?q=Cells,%20Cultured","dc:title":"Cells, Cultured"}],"relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1390001205521729920","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"骨粗鬆症を伴う要介護高齢者に対するアレンドロネート長期投与による歯周組織変化"},{"@language":"en","@value":"The Change of Periodontal Tissue of Elderly People in a Long-term Facility by Long-term Administration of Alendronate"}]},{"@id":"https://cir.nii.ac.jp/crid/1390282679391871232","@type":"Article","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"Consideration of periodontal treatment planing for a patient in oral bisphosphonate therapy"},{"@language":"ja","@value":"ビスホスホネート投与患者に対する歯周治療の１例から治療計画を再考する"}]},{"@id":"https://cir.nii.ac.jp/crid/1570854176746153216","@type":"Article","relationType":["isCitedBy"],"jpcoar:relatedTitle":[{"@language":"ja","@value":"歯周病罹患歯歯根膜における非コラーゲン性タンパク質の分解と好中球エラスターゼについて"},{"@language":"en","@value":"Degradation of Non-Collagenous Proteins and Neutrophil Elastase in Diseased Peridontal Ligament"}]}],"dataSourceIdentifier":[{"@type":"CROSSREF","@value":"10.1902/jop.2000.71.7.1158"},{"@type":"CIA","@value":"30015371801"},{"@type":"OPENAIRE","@value":"doi_dedup___::fbd8186df69c63dae70d20431c19ac97"},{"@type":"CROSSREF","@value":"10.2329/perio.54.346_references_DOI_KdHJWuBcZD29eZ92lc1aK7moKaQ"}]}