Patrão, Mariana RamosPereira, Pedro MarianoCaldeira, JorgeSalema-Oom, Madalena2026-03-192026-03-192026-01-051661-6596PURE: 157103189PURE UUID: f08b56c4-edbe-4823-81b7-de90feb6cecaScopus: 105027054818PubMed: 41516413PubMedCentral: PMC12787207WOS: 001657399600001http://hdl.handle.net/10362/201657Publisher Copyright: © 2026 by the authors.Matrix metallopeptidases (MMPs) are enzymes that, in balance with their inhibitors, play a vital role in extracellular matrix remodelling, particularly during orthodontic tooth movement (OTM). Despite growing interest, significant research is still required to fully comprehend the mechanisms and signalling pathways involved in periodontal ligament remodelling and OTM, particularly those mediated by MMPs. This review explores recent in vitro and in vivo evidence on how specific MMPs—namely, MMP-1, -2, -3, -8, -9, -12, -13, and -14—respond to compressive and tensile forces, regulate collagen degradation, and influence periodontal ligament fibroblast and osteoblast behaviour, ultimately shaping tissue resorption and formation. We also summarize the roles of periodontal ligament cells, hypoxia, the neurovascular and immune systems, and well-known molecules—including receptor activator of nuclear factor kappa β, receptor activator of nuclear factor kappa β ligand, osteoprotegerin, macrophage colony-stimulating factor, tumour necrosis factor α, transforming growth factor, and interleukins—in orchestrating these responses. Finally, we address the clinical relevance of these pathways, highlighting the potential for therapeutic strategies targeting MMPs activity. Overall, this review underscores the pivotal contribution of MMPs to extracellular matrix turnover and tissue adaptation during OTM and suggests that modulating the MMPs/tissue inhibitors of matrix metallopeptidase (TIMPs) balance may enhance orthodontic outcomes.231295264engCompression sideMatrix metallopeptidasesOrthodontic tooth movementPeriodontal ligamentTension sideCatalysisMolecular BiologyComputer Science ApplicationsSpectroscopyPhysical and Theoretical ChemistryOrganic ChemistryInorganic Chemistryreview10.3390/ijms27010542https://www.scopus.com/pages/publications/105027054818https://www.webofscience.com/wos/woscc/full-record/WOS:001657399600001