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It enables smooth movement, distributes mechanical loads, and protects the underlying bone. In response to loading, AC adapts by modifying both its thickness and composition. AC is organised in different zones, with low cellularity and a high abundance of extracellular matrix (ECM). Mechanical overloading or immobilisation can lead to structural changes, potentially resulting in osteoarthritis (OA), for which no causal treatment currently exists. However, smaller defects can be treated using chondrocyte\/cartilage transplantation or tissue engineering. A better understanding of the molecular composition of AC at different locations is essential to improve such therapeutic approaches. For this purpose, we performed a comprehensive analysis of porcine femoral knee cartilage at eight defined anatomical sites. Cartilage thickness and proteoglycan (PG) content were analysed histologically, while specific ECM proteins were assessed by proteomics and validated by immunohistochemistry and Western blot. Significant differences were identified, particularly between medial and lateral compartments, in terms of cartilage thickness, PG abundance, and ECM composition. Some proteins also showed zone-specific localisation patterns. These structural differences likely reflect adaptation to mechanical loading and should be considered to optimise future cartilage repair and tissue engineering strategies.<\/jats:p>","DOI":"10.3390\/ijms26199331","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T08:56:44Z","timestamp":1758790604000},"page":"9331","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Localisation-Dependent Variations in Articular Cartilage ECM: Implications for Tissue Engineering and Cartilage Repair"],"prefix":"10.3390","volume":"26","author":[{"given":"Laura","family":"Weimer","sequence":"first","affiliation":[{"name":"Faculty 2: Computer Science and Engineering, Frankfurt University of Applied Sciences, 60318 Frankfurt, Germany"},{"name":"Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9805-4941","authenticated-orcid":false,"given":"Luisa M.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), and Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany"},{"name":"Novo Nordisk Foundation Center for Protein Research, Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 1172 Copenhagen, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerhard","family":"Sengle","sequence":"additional","affiliation":[{"name":"Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, Center for Biochemistry, Center for Molecular Medicine Cologne (CMMC), Cologne Center for Musculoskeletal Biomechanics (CCMB), and Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5846-6941","authenticated-orcid":false,"given":"Marcus","family":"Kr\u00fcger","sequence":"additional","affiliation":[{"name":"Institute for Genetics, Cologne Excellence Cluster on Cellular Stress Responses in Ageing-Associated Diseases (CECAD), and Center for Molecular Medicine Cologne (CMMC), University of Cologne, 50931 Cologne, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2791-3208","authenticated-orcid":false,"given":"Alan M.","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield HD1 3DH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ilona","family":"Br\u00e4ndlin","sequence":"additional","affiliation":[{"name":"Faculty 2: Computer Science and Engineering, Frankfurt University of Applied Sciences, 60318 Frankfurt, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7680-9354","authenticated-orcid":false,"given":"Frank","family":"Zaucke","sequence":"additional","affiliation":[{"name":"Dr. Rolf M. 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