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Decorin regulates cartilage pericellular matrix micromechanobiology
Journal article   Open access   Peer reviewed

Decorin regulates cartilage pericellular matrix micromechanobiology

Daphney R. Chery, Biao Han, Ying Zhou, Chao Wang, Sheila M. Adams, Prashant Chandrasekaran, Bryan Kwok, Su-Jin Heo, Motomi Enomoto-Iwamoto, X. Lucas Lu, …
Matrix biology, v 96, pp 1-17
Feb 2021
DOI: https://doi.org/10.1016/j.matbio.2020.11.002
PMID: 33246102
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902451View
Accepted (AM)Open Access (License Unspecified),  Open

Abstract

Chondrocyte Decorin Mechanotransduction Nanomechanics Pericellular matrix
•Decorin regulates the aggrecan network integrity and micromechanics of cartilage pericellular matrix.•The highly negative charged osmotic microenvironment of pericellular matrix is required for normal chondrocyte mechanotransduction in situ.•Decorin affects the intracellular calcium signaling of chondrocytes by mediating the aggrecan-endowed osmotic microenvironment of pericellular matrix.•The impact of decorin loss on the disruption of chondrocyte mechanobiology is increasingly aggravated during maturation. In cartilage tissue engineering, one key challenge is for regenerative tissue to recapitulate the biomechanical functions of native cartilage while maintaining normal mechanosensitive activities of chondrocytes. Thus, it is imperative to discern the micromechanobiological functions of the pericellular matrix, the ~ 2–4 µm-thick domain that is in immediate contact with chondrocytes. In this study, we discovered that decorin, a small leucine-rich proteoglycan, is a key determinant of cartilage pericellular matrix micromechanics and chondrocyte mechanotransduction in vivo. The pericellular matrix of decorin-null murine cartilage developed reduced content of aggrecan, the major chondroitin sulfate proteoglycan of cartilage and a mild increase in collagen II fibril diameter vis-à-vis wild-type controls. As a result, decorin-null pericellular matrix showed a significant reduction in micromodulus, which became progressively more pronounced with maturation. In alignment with the defects of pericellular matrix, decorin-null chondrocytes exhibited decreased intracellular calcium activities, [Ca2+]i, in both physiologic and osmotically evoked fluidic environments in situ, illustrating impaired chondrocyte mechanotransduction. Next, we compared [Ca2+]i activities of wild-type and decorin-null chondrocytes following enzymatic removal of chondroitin sulfate glycosaminoglycans. The results showed that decorin mediates chondrocyte mechanotransduction primarily through regulating the integrity of aggrecan network, and thus, aggrecan-endowed negative charge microenvironment in the pericellular matrix. Collectively, our results provide robust genetic and biomechanical evidence that decorin is an essential constituent of the native cartilage matrix, and suggest that modulating decorin activities could improve cartilage regeneration.

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Collaboration types
Domestic collaboration
International collaboration
Web of Science research areas
Biochemistry & Molecular Biology
Cell Biology
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