{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T20:20:40Z","timestamp":1792700440579,"version":"4.5.0"},"reference-count":173,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T00:00:00Z","timestamp":1644364800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The aim of this study was to highlight the roles of perlecan in the regulation of the development of the rudiment developmental cartilages and growth plate cartilages, and also to show how perlecan maintains permanent articular cartilage homeostasis. Cartilage rudiments are transient developmental templates containing chondroprogenitor cells that undergo proliferation, matrix deposition, and hypertrophic differentiation. Growth plate cartilage also undergoes similar changes leading to endochondral bone formation, whereas permanent cartilage is maintained as an articular structure and does not undergo maturational changes. Pericellular and extracellular perlecan-HS chains interact with growth factors, morphogens, structural matrix glycoproteins, proteases, and inhibitors to promote matrix stabilization and cellular proliferation, ECM remodelling, and tissue expansion. Perlecan has mechanotransductive roles in cartilage that modulate chondrocyte responses in weight-bearing environments. Nuclear perlecan may modulate chromatin structure and transcription factor access to DNA and gene regulation. Snail-1, a mesenchymal marker and transcription factor, signals through FGFR-3 to promote chondrogenesis and maintain Acan and type II collagen levels in articular cartilage, but prevents further tissue expansion. Pre-hypertrophic growth plate chondrocytes also express high Snail-1 levels, leading to cessation of Acan and CoI2A1 synthesis and appearance of type X collagen. Perlecan differentially regulates FGF-2 and FGF-18 to maintain articular cartilage homeostasis, rudiment and growth plate cartilage growth, and maturational changes including mineralization, contributing to skeletal growth.<\/jats:p>","DOI":"10.3390\/ijms23041934","type":"journal-article","created":{"date-parts":[[2022,2,9]],"date-time":"2022-02-09T21:22:15Z","timestamp":1644441735000},"page":"1934","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Regulation of FGF-2, FGF-18 and Transcription Factor Activity by Perlecan in the Maturational Development of Transitional Rudiment and Growth Plate Cartilages and in the Maintenance of Permanent Cartilage Homeostasis"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2918-3723","authenticated-orcid":false,"given":"Anthony J.","family":"Hayes","sequence":"first","affiliation":[{"name":"Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Whitelock","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW 2052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9237-0524","authenticated-orcid":false,"given":"James","family":"Melrose","sequence":"additional","affiliation":[{"name":"Graduate School of Biomedical Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW 2052, Australia"},{"name":"Raymond Purves Bone and Joint Research Laboratory, Kolling Institute of Medical Research, Northern Sydney Area Local Health District, St. Leonards, NSW 2065, Australia"},{"name":"Sydney Medical School, Northern, Faculty of Medicine and Health, The University of Sydney, Royal North Shore Hospital, St. Leonards, NSW 2065, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"105849","DOI":"10.1016\/j.biocel.2020.105849","article-title":"Perlecan, a Modular Instructive Proteoglycan with Diverse Functional Properties","volume":"128","author":"Melrose","year":"2020","journal-title":"Int. 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