Bioimaging Research Hub, Cardiff School of Biosciences, Cardiff University, Cardiff CF10 3AX, Wales, UK.
Graduate School of Biomedical Engineering, Faculty of Engineering, University of New South Wales, Sydney, NSW 2052, Australia.
Int J Mol Sci. 2022 Feb 9;23(4):1934. doi: 10.3390/ijms23041934.
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.
本研究旨在强调核心蛋白聚糖在胚性软骨和生长板软骨发育调控中的作用，并展示核心蛋白聚糖如何维持永久性关节软骨的稳态。软骨原基是包含软骨祖细胞的短暂性发育模板，这些细胞经历增殖、基质沉积和肥大分化。生长板软骨也经历类似的变化，导致软骨内骨形成，而永久性软骨作为关节结构保持不变，不经历成熟性变化。细胞周和细胞外核心蛋白聚糖-HS 链与生长因子、形态发生素、结构基质糖蛋白、蛋白酶和抑制剂相互作用，促进基质稳定和细胞增殖、ECM 重塑和组织扩张。核心蛋白聚糖在软骨中具有机械转导作用，调节承重环境中软骨细胞的反应。核核心蛋白聚糖可能调节染色质结构和转录因子对 DNA 的访问以及基因调控。Snail-1 是一种间充质标志物和转录因子，通过 FGFR-3 信号传导促进软骨生成，并维持关节软骨中的 Acan 和 II 型胶原水平，但防止进一步的组织扩张。预肥大生长板软骨细胞也表达高水平的 Snail-1，导致 Acan 和 CoI2A1 合成停止，出现 X 型胶原。核心蛋白聚糖通过差异调节 FGF-2 和 FGF-18 来维持关节软骨稳态、胚性和生长板软骨生长以及包括矿化在内的成熟性变化，为骨骼生长做出贡献。
