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This comprehensive review examines the pathogenic mechanisms, diagnostic applications, and therapeutic targeting potential of the entire MMP family in periodontitis and peri\u2010implantitis. All MMP subfamilies, collagenases (MMP\u20101, \u20108, \u201013), gelatinases (MMP\u20102, \u20109), stromelysins (MMP\u20103, \u201010, \u201011), matrilysins (MMP\u20107, \u201026), membrane\u2010type MMPs (MT1\u20106), and others, demonstrate distinct expression patterns and substrate specificities in diseased tissues. MMP\u20108 and MMP\u20109 emerge as primary biomarkers, showing 5\u20136\u2010fold elevations in active periodontitis compared to health, with corresponding increases in activation ratios and decreases in tissue inhibitor of metalloproteinase (TIMP) levels. Diagnostic applications reveal point\u2010of\u2010care active MMP\u20108 (aMMP\u20108) immunotests achieve 70%\u201385% sensitivity and 65%\u201380% specificity for periodontitis detection, though standardization challenges limit clinical implementation. Salivary and gingival crevicular fluid MMP profiling demonstrates disease\u2010specific signatures, with MMP\u20108\/TIMP\u20101 ratios serving as progression indicators. Therapeutically, MMP modulation strategies include FDA\u2010approved subantimicrobial dose doxycycline (SDD), which achieves a 40%\u201360% reduction in clinical attachment loss. Novel approaches encompass selective MMP inhibitors, pro\u2010resolving mediators, and host\u2010modulation therapies, with emerging AI\u2010assisted personalized treatment protocols showing promise. Critically, peri\u2010implantitis exhibits more severe MMP dysregulation than periodontitis, with MMP: TIMP ratios reaching 50:1 versus 20:1, accelerated bone loss patterns, and distinct MT\u2010MMP involvement reflecting titanium surface interactions. Translation barriers include the need for biomarker standardization, the complexity of MMP redundancy, and the requirement for personalized diagnostic thresholds. Future directions emphasize integrating MMP signatures with multi\u2010omics approaches, developing selective inhibitors, and establishing evidence\u2010based clinical guidelines for MMP\u2010targeted precision periodontal medicine.<\/jats:p>","DOI":"10.1111\/jre.70062","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:40:26Z","timestamp":1768912826000},"page":"355-371","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Matrix Metalloproteinases in Periodontal and Peri\u2010Implant Diseases: Contribution to Their Pathogenesis, Diagnosis, and Treatment"],"prefix":"10.1111","volume":"61","author":[{"given":"Timo","family":"Sorsa","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases University of Helsinki and Helsinki University Hospital  Helsinki Finland"},{"name":"Department of Dental Medicine Karolinska Institutet  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorne M.","family":"Golub","sequence":"additional","affiliation":[{"name":"Department of Oral Biology &amp; Pathology, School of Dental Medicine Stony Brook University  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6390-2621","authenticated-orcid":false,"given":"Julie Toby","family":"Thomas","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Diseases University of Helsinki and Helsinki University Hospital  Helsinki Finland"},{"name":"Department of Periodontics, Saveetha Dental College and Hospitals Saveetha Institute of Medical and Technical Sciences  Chennai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Leone","sequence":"additional","affiliation":[{"name":"Private Practice  Naples Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6440-8780","authenticated-orcid":false,"given":"Sukumaran","family":"Anil","sequence":"additional","affiliation":[{"name":"Oral Health Institute Hamad Medical Corporation  Doha Qatar"},{"name":"College of Dental Medicine Qatar University  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veli\u2010Jukka","family":"Uitto","sequence":"additional","affiliation":[{"name":"Department of Oral Biological and Medical Sciences, Faculty of Dentistry University of British Columbia  Vancouver British Columbia Canada"},{"name":"Department of Oral and Maxillofacial Surgery Helsinki University Central Hospital  Helsinki Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,20]]},"reference":[{"key":"e_1_2_15_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.38"},{"key":"e_1_2_15_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12903-025-06271-0"},{"key":"e_1_2_15_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13337"},{"key":"e_1_2_15_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0022034514552491"},{"key":"e_1_2_15_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/jre.13421"},{"key":"e_1_2_15_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12101"},{"key":"e_1_2_15_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12334"},{"key":"e_1_2_15_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcpe.12954"},{"key":"e_1_2_15_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1517154"},{"key":"e_1_2_15_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12104"},{"key":"e_1_2_15_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41579-018-0089-x"},{"key":"e_1_2_15_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/prd.12002"},{"key":"e_1_2_15_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/JPER.18-0006"},{"issue":"20","key":"e_1_2_15_15_1","first-page":"S1","article-title":"A New Classification Scheme for Periodontal and Peri\u2010Implant Diseases and Conditions \u2010 Introduction and Key Changes From the 1999 Classification","volume":"45","author":"Caton J. 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