Perlecan in pericellular mechanosensory cell-matrix communication, extracellular matrix stabilisation and mechanoregulation of load-bearing connective tissues

Guilak, Farshid, Hayes, Anthony J. and Melrose, James 2021. Perlecan in pericellular mechanosensory cell-matrix communication, extracellular matrix stabilisation and mechanoregulation of load-bearing connective tissues. International Journal of Molecular Sciences 22 (5) , 2716. 10.3390/ijms22052716

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Abstract

In this study, we review mechanoregulatory roles for perlecan in load-bearing connective tissues. Perlecan facilitates the co-acervation of tropoelastin and assembly of elastic microfibrils in translamellar cross-bridges which, together with fibrillin and elastin stabilise the extracellular matrix of the intervertebral disc annulus fibrosus. Pericellular perlecan interacts with collagen VI and XI to define and stabilize this matrix compartment which has a strategic position facilitating two-way cell-matrix communication between the cell and its wider extracellular matrix. Cues from the extracellular matrix are fed through this pericellular matrix back to the chondrocyte, allowing it to perceive and respond to subtle microenvironmental changes to regulate tissue homeostasis. Thus perlecan plays a key regulatory role in chondrocyte metabolism, and in chondrocyte differentiation. Perlecan acts as a transport proteoglycan carrying poorly soluble, lipid-modified proteins such as the Wnt or Hedgehog families facilitating the establishment of morphogen gradients that drive tissue morphogenesis. Cell surface perlecan on endothelial cells or osteocytes acts as a flow sensor in blood and the lacunar canalicular fluid providing feedback cues to smooth muscle cells regulating vascular tone and blood pressure, and the regulation of bone metabolism by osteocytes highlighting perlecan’s multifaceted roles in load-bearing connective tissues.

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:	17 March 2021
Date of Acceptance:	5 March 2021
Last Modified:	05 May 2023 01:33
URI:	https://orca.cardiff.ac.uk/id/eprint/139875

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