The Extracellular Matrix of Articular Cartilage Controls the Bioavailability of Pericellular Matrix-Bound Growth Factors to Drive Tissue Homeostasis and Repair

Vincent, Tonia L., McClurg, Oliver and Troeberg, Linda (2022) The Extracellular Matrix of Articular Cartilage Controls the Bioavailability of Pericellular Matrix-Bound Growth Factors to Drive Tissue Homeostasis and Repair. International Journal of Molecular Sciences, 23 (11). ISSN 1661-6596

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Abstract

The extracellular matrix (ECM) has long been regarded as a packing material; supporting cells within the tissue and providing tensile strength and protection from mechanical stress. There is little surprise when one considers the dynamic nature of many of the individual proteins that contribute to the ECM, that we are beginning to appreciate a more nuanced role for the ECM in tissue homeostasis and disease. Articular cartilage is adapted to be able to perceive and respond to mechanical load. Indeed, physiological loads are essential to maintain cartilage thickness in a healthy joint and excessive mechanical stress is associated with the breakdown of the matrix that is seen in osteoarthritis (OA). Although the trigger by which increased mechanical stress drives catabolic pathways remains unknown, one mechanism by which cartilage responds to increased compressive load is by the release of growth factors that are sequestered in the pericellular matrix. These are heparan sulfate-bound growth factors that appear to be largely chondroprotective and displaced by an aggrecan-dependent sodium flux. Emerging evidence suggests that the released growth factors act in a coordinated fashion to drive cartilage repair. Thus, we are beginning to appreciate that the ECM is the key mechano-sensor and mechano-effector in cartilage, responsible for directing subsequent cellular events of relevance to joint health and disease.

Item Type: Article
Additional Information: Funding Information: Conflicts of Interest: T.L.V. receives grant support from Pfizer, Galapagos, Fidia, Biosplice, and Novartis for the STEpUP OA Consortium. Funding Information: Funding: T.L.V. directs the Centre for OA Pathogenesis Versus Arthritis (grant nos. 20205 and 21621). O.M. and L.T. are supported by Versus Arthritis grants 22194 and 21776. Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Uncontrolled Keywords: articular cartilage,extracellular matrix,growth factors,heparan sulfate,mechanotransduction,osteoarthritis,pericellular matrix,perlecan,catalysis,molecular biology,spectroscopy,computer science applications,physical and theoretical chemistry,organic chemistry,inorganic chemistry ,/dk/atira/pure/subjectarea/asjc/1500/1503
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
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Depositing User: LivePure Connector
Date Deposited: 16 Jun 2022 14:30
Last Modified: 19 Jun 2022 06:30
URI: https://ueaeprints.uea.ac.uk/id/eprint/85659
DOI: 10.3390/ijms23116003

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