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Review

Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage

Biomechanics and Bioengineering Centre Versus Arthritis, School of Biosciences, Cardiff University, Cardiff CF10 3AX, UK
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Academic Editor: James Melrose
Int. J. Mol. Sci. 2021, 22(24), 13595; https://doi.org/10.3390/ijms222413595
Received: 18 November 2021 / Revised: 8 December 2021 / Accepted: 15 December 2021 / Published: 18 December 2021
The composition and organisation of the extracellular matrix (ECM), particularly the pericellular matrix (PCM), in articular cartilage is critical to its biomechanical functionality; the presence of proteoglycans such as aggrecan, entrapped within a type II collagen fibrillar network, confers mechanical resilience underweight-bearing. Furthermore, components of the PCM including type VI collagen, perlecan, small leucine-rich proteoglycans—decorin and biglycan—and fibronectin facilitate the transduction of both biomechanical and biochemical signals to the residing chondrocytes, thereby regulating the process of mechanotransduction in cartilage. In this review, we summarise the literature reporting on the bidirectional reciprocity of the ECM in chondrocyte mechano-signalling and articular cartilage homeostasis. Specifically, we discuss studies that have characterised the response of articular cartilage to mechanical perturbations in the local tissue environment and how the magnitude or type of loading applied elicits cellular behaviours to effect change. In vivo, including transgenic approaches, and in vitro studies have illustrated how physiological loading maintains a homeostatic balance of anabolic and catabolic activities, involving the direct engagement of many PCM molecules in orchestrating this slow but consistent turnover of the cartilage matrix. Furthermore, we document studies characterising how abnormal, non-physiological loading including excessive loading or joint trauma negatively impacts matrix molecule biosynthesis and/or organisation, affecting PCM mechanical properties and reducing the tissue’s ability to withstand load. We present compelling evidence showing that reciprocal engagement of the cells with this altered ECM environment can thus impact tissue homeostasis and, if sustained, can result in cartilage degradation and onset of osteoarthritis pathology. Enhanced dysregulation of PCM/ECM turnover is partially driven by mechanically mediated proteolytic degradation of cartilage ECM components. This generates bioactive breakdown fragments such as fibronectin, biglycan and lumican fragments, which can subsequently activate or inhibit additional signalling pathways including those involved in inflammation. Finally, we discuss how bidirectionality within the ECM is critically important in enabling the chondrocytes to synthesise and release PCM/ECM molecules, growth factors, pro-inflammatory cytokines and proteolytic enzymes, under a specified load, to influence PCM/ECM composition and mechanical properties in cartilage health and disease. View Full-Text
Keywords: articular cartilage; mechanobiology; extracellular/pericellular matrix; homeostatic balance; osteoarthritis articular cartilage; mechanobiology; extracellular/pericellular matrix; homeostatic balance; osteoarthritis
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MDPI and ACS Style

Gilbert, S.J.; Bonnet, C.S.; Blain, E.J. Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage. Int. J. Mol. Sci. 2021, 22, 13595. https://doi.org/10.3390/ijms222413595

AMA Style

Gilbert SJ, Bonnet CS, Blain EJ. Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage. International Journal of Molecular Sciences. 2021; 22(24):13595. https://doi.org/10.3390/ijms222413595

Chicago/Turabian Style

Gilbert, Sophie Jane, Cleo Selina Bonnet, and Emma Jane Blain. 2021. "Mechanical Cues: Bidirectional Reciprocity in the Extracellular Matrix Drives Mechano-Signalling in Articular Cartilage" International Journal of Molecular Sciences 22, no. 24: 13595. https://doi.org/10.3390/ijms222413595

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