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

Hayes, Anthony J., Whitelock, John and Melrose, James 2022. 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. International Journal of Molecular Sciences 23 (4) , 1934. 10.3390/ijms23041934

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Additional Information:	This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/)
Publisher:	MDPI
ISSN:	1422-0067
Date of First Compliant Deposit:	5 July 2022
Date of Acceptance:	1 February 2022
Last Modified:	12 May 2023 20:31
URI:	https://orca.cardiff.ac.uk/id/eprint/151052

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