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. 2024 Jan 31;44(1):BSR20231730.
doi: 10.1042/BSR20231730.

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Jing Song  1 , Xuemin Zeng  2 , Chenzhi Li  2 , Hongyan Yin  3 , Sui Mao  3 , Dapeng Ren  2
Affiliations

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis

Jing Song et al. Biosci Rep. .

Abstract

Osteoarthritis (OA) is characterized by cartilage degeneration and destruction, leading to joint ankylosis and disability. The major challenge in diagnosing OA at early stage is not only lack of clinical symptoms but also the insufficient histological and immunohistochemical signs. Alteration in cartilage stiffness during OA progression, especially at OA initiation, has been confirmed by growing evidences. Moreover, the stiffness of cartilage extracellular matrix (ECM), pericellular matrix (PCM) and chondrocytes during OA development are dynamically changed in unique and distinct fashions, revealing possibly inconsistent conclusions when detecting cartilage matrix stiffness at different locations and scales. In addition, it will be discussed regarding the mechanisms through which OA-related cartilage degenerations exhibit stiffened or softened matrix, highlighting some critical events that generally incurred to cartilage stiffness alteration, as well as some typical molecules that participated in constituting the mechanical properties of cartilage. Finally, in vitro culturing chondrocytes in various stiffness-tunable scaffolds provided a reliable method to explore the matrix stiffness-dependent modulation of chondrocyte metabolism, which offers valuable information on optimizing implant scaffolds to maximally promote cartilage repair and regeneration during OA. Overall, this review systematically and comprehensively elucidated the current progresses in the relationship between cartilage stiffness alteration and OA progression. We hope that deeper attention and understanding in this researching field will not only develop more innovative methods in OA early detection and diagnose but also provide promising ideas in OA therapy and prognosis.

Keywords: cartilage; matrix stiffness; osteoarthritis.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Matrix molecules constituting cartilage matrix stiffness
Major matrix molecules in cartilage matrix that has been reported to be related with cartilage stiffness. Some of these, such as collagen VI and perlecan, were found exclusively in cartilage PCM, while other molecules like collagen II, collagen IX, aggrecan, decorin and chondroadherin were found predominately in cartilage ECM. These molecules covalently bond with each other, which together constitute cartilage matrix stiffness.
Figure 2
Figure 2. Mechanisms of matrix stiffness in regulating chondrocyte metabolism
Scaffolds with distinct stiffness affected chondrocyte metabolism through mechanisms of either canonical mechano-transduction pathways such as laminin β1-FAK, RhoA-ROCK or Ca2+ channels TRPV4, TRPA1, Piezo1/2 and epigenetic modifications. Downstream events include phosphorylation of YAP, MLC, Smad3 and GSK3β, which activate genes involved in cytoskeleton reorganization, inflammation and metabolism of chondrocytes
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References

    1. Zhu X.et al. . (2020) Subchondral bone remodeling: a therapeutic target for osteoarthritis. Front Cell Dev. Biol. 8, 607764 10.3389/fcell.2020.607764 - DOI - PMC - PubMed
    1. Battistelli M.et al. . (2019) Morphological and ultrastructural analysis of normal, injured and osteoarthritic human knee menisci. Eur. J. Histochem. 63, 17–23 10.4081/ejh.2019.2998 - DOI - PMC - PubMed
    1. Ozeki N., Koga H. and Sekiya I. (2022) Degenerative meniscus in knee osteoarthritis: from pathology to treatment. Life (Basel) 12, 603–617 10.3390/life12040603 - DOI - PMC - PubMed
    1. Favero M.et al. . (2017) Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study. Rheumatology (Oxford). 56, 1784–1793 10.1093/rheumatology/kex287 - DOI - PubMed
    1. Kalamegam G.et al. . (2018) A Comprehensive Review of Stem Cells for Cartilage Regeneration in Osteoarthritis. Adv. Exp. Med. Biol. 1089, 23–36 10.1007/5584_2018_205 - DOI - PubMed

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