Deciphering pathological remodelling of the human cartilage extracellular matrix in osteoarthritis at the supramolecular level

Jaabar, Ilhem Lilia; Cornette, Pascale; Miche, Antoine; Wanherdrick, Kristell; Duprès, Vincent; Ehkirch, F.-P.; Binder, Annette; Bérenbaum, Francis; Houard, Xavier; Landoulsi, Jessem

doi:10.1039/d2nr00474g

Cited by 13 publications

(7 citation statements)

References 49 publications

(96 reference statements)

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“…During OA, the mineralisation inhibitors in cartilage ECM (proteoglycans and collagen-II) were degraded, and the promotors (collagen-I, collagen-X and Runx-2) were increased 2 30. Such degradation process further induced disruption of collagen fibrils (bundle-like structures shown in figure 1 and online supplemental figure S5),31 32 and provided space for calcium phosphate deposition in OA cartilage. The structural and compositional alterations in cartilage ECM may partially increase the local concentrations of Ca 2+ and PO 4 3− ,33 thereby developing to unfavourable mineral formation in OA cartilage 2.…”

Section: Discussionmentioning

confidence: 99%

Stage-specific and location-specific cartilage calcification in osteoarthritis development

Wang

Zhang

et al. 2022

Ann Rheum Dis

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ObjectivesThis study investigated the stage-specific and location-specific deposition and characteristics of minerals in human osteoarthritis (OA) cartilages via multiple nano-analytical technologies.MethodsNormal and OA cartilages were serially sectioned for micro-CT, scanning electron microscopy with energy dispersive X-ray spectroscopy, micro-Raman spectroscopy, focused ion beam scanning electron microscopy, high-resolution electron energy loss spectrometry with transmission electron microscopy, nanoindentation and atomic force microscopy to analyse the structural, compositional and mechanical properties of cartilage in OA progression.ResultsWe found that OA progressed by both top-down calcification at the joint surface and bottom-up calcification at the osteochondral interface. The top-down calcification process started with spherical mineral particle formation in the joint surface during early-stage OA (OA-E), followed by fibre formation and densely packed material transformation deep into the cartilage during advanced-stage OA (OA-A). The bottom-up calcification in OA-E started when an excessive layer of calcified tissue formed above the original calcified cartilage, exhibiting a calcified sandwich structure. Over time, the original and upper layers of calcified cartilage fused, which thickened the calcified cartilage region and disrupted the cartilage structure. During OA-E, the calcified cartilage was hypermineralised, containing stiffer carbonated hydroxyapatite (HAp). During OA-A, it was hypomineralised and contained softer HAp. This discrepancy may be attributed to matrix vesicle nucleation during OA-E and carbonate cores during OA-A.ConclusionsThis work refines our current understanding of the mechanism underlying OA progression and provides the foothold for potential therapeutic targeting strategies once the location-specific cartilage calcification features in OA are established.

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Section: Discussionmentioning

confidence: 99%

Stage-specific and location-specific cartilage calcification in osteoarthritis development

Wang

Zhang

et al. 2022

Ann Rheum Dis

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“…They are living in a state of low oxygen pressure (< 5% O 2 , compared to > 12% O 2 in arterial blood) and low metabolic activity, and they intake nutrients mainly through the diffusion of surrounding tissues due to lack of support from blood capillaries, nerves and microlymphatic vessels. [ 6 ] However, although chondrocytes account for less than 10% of the cartilage volume (≈2 wt%), they are responsible for the formation, maintenance, and remodeling of the entire cartilage matrix. Chondrocytes synthesize and secrete tissue‐specific collagens, including types II, III, VI, IX, X, XI, XII, and XIV.…”

Section: Introductionmentioning

confidence: 99%

“…[ 9 ] As the most abundant proteoglycan, aggrecan, combined with CSs, KSs, and DSs, participates forming the core protein backbone of the meshwork‐like matrix by covalent binding. [ 6 ] However, aggrecans are only present in the cartilage ECM as free‐standing aggregates, and they are noncovalently attached to the peripheral long GAG chains through some linking proteins to form larger aggregates. These aggregates embed into the interfibrillar space of heterotypic collagen fibrils and draw a large amount of water (≈65–85 wt%) into the cartilage meshwork‐like matrix, which results in the generation of osmotic swelling pressure that is offset by the tensile strength of collagen fibrils.…”

Section: Introductionmentioning

confidence: 99%

“…[ 18 ] Previous reports have indicated that global ECM stiffening occurs during the transition from healthy to OA cartilage and with increasing in the Young's moduli and Mankin scores. [ 6 ] A nanoindentation test based on atomic force microscope (AFM) further provided evidence that the nanomechanical property changes of cartilage were correlated with supramolecular changes at the level of individual collagen fibrils. [ 19 ] In addition, the increase in ECM stiffness due to local fibrosis caused by the enhanced generation of type I collagen and osteophyte formation due to accelerated abnormal ossification are the hallmarks of OA progression.…”

Section: Introductionmentioning

confidence: 99%

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Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate via Mechanoadaptability

Zhou,

Yang,

Duan

et al. 2023

Adv Healthcare Materials

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It is recognized that the changes in the physical properties of extracellular matrix result in fine‐tuned cell responses including cell morphology, proliferation and differentiation. In this study, a novel patterned equidistant micropillar substrate based on polydimethylsiloxane (PDMS) was designed to mimic the collagen fiber‐like network of the cartilage matrix. By changing the component of the curing agent to an oligomeric base, we obtained micropillar substrates with the same topology but different stiffnesses and found that chondrocytes seeded onto the soft micropillar substrate maintain their phenotype by gathering type II collagen and aggrecan more effectively than those seeded onto the stiff micropillar substrate. Moreover, chondrocytes sensed and responded to micropillar substrates with different stiffnesses by altering the ECM‐cytoskeleton‐focal adhesion axis. We then found that the soft substrate‐preserved chondrocyte phenotype was dependent on the activation of Wnt/β‐catenin signaling at a high expression level. Finally, we indicated the changes in osteoid‐like region formation and cartilage phenotype loss in the stiffened sclerotic area of osteoarthritis mouse cartilage to validate the cell behavior changes triggered by micropillar substrates with different stiffnesses. This study provided the change in cell behaviors that are more similar to those of real chondrocytes at tissue level during the transition from a normal state to a state of osteoarthritis.This article is protected by copyright. All rights reserved

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“…Throughout the appearance of OA, the ECM is put through a compound of chemical and structural modifications that are essential in the start and the advancement of the illness. Although the molecular processes implicated in the pathological remodeling of the ECM are deemed as critical, they remain, nevertheless, not entirely clarified [9].…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms of Cartilage Repair and Their Possible Clinical Uses: A Review of Recent Developments

Rodríguez-Merchán

2022

IJMS

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Articular cartilage (AC) defects are frequent but hard to manage. Osteoarthritis (OA) is a musculoskeletal illness that afflicts between 250 and 500 million people in the world. Even though traditional OA drugs can partly alleviate pain, these drugs cannot entirely cure OA. Since cartilaginous tissue of the joints has a poor self-repair capacity and very poor proliferative ability, the healing of injured cartilaginous tissue of the joint has not been accomplished so far. Consequently, the discovery of efficacious mediations and regenerative treatments for OA is needed. This manuscript reviews the basic concepts and the recent developments on the molecular mechanisms of cartilage repair and their potential clinical applications. For this purpose, a literature exploration was carried out in PubMed for the years 2020, 2021, and 2022. On 31 October 2022 and using “cartilage repair molecular mechanisms” as keywords, 41 articles were found in 2020, 42 in 2021, and 36 in 2022. Of the total of 119 articles, 80 were excluded as they were not directly related to the title of this manuscript. Of particular note are the advances concerning the mechanisms of action of hyaluronic acid, mesenchymal stem cells (MSCs), nanotechnology, enhancer of zeste 2 polycomb repressive complex 2 subunit (EHZ2), hesperetin, high mobility group box 2 (HMGB2), α2-macroglobulin (α2M), proteoglycan 4 (Prg4)/lubricin, and peptides related to cartilage repair and treatment of OA. Despite the progress made, current science has not yet achieved a definitive solution for healing AC lesions or repairing cartilage in the case of OA. Therefore, further research into the molecular mechanisms of AC damage is needed in the coming decades.

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Deciphering pathological remodelling of the human cartilage extracellular matrix in osteoarthritis at the supramolecular level

Abstract: The extracellular matrix (ECM) of articular cartilage is a three-dimensional network mainly constituted of entangled collagen fibrils and interfibrillar aggrecan aggregates. During the development of osteoarthrosis (OA), the most common...

Cited by 13 publications

References 49 publications

Stage-specific and location-specific cartilage calcification in osteoarthritis development

Stage-specific and location-specific cartilage calcification in osteoarthritis development

Biomimetic Fibers Based on Equidistant Micropillar Arrays Determines Chondrocyte Fate via Mechanoadaptability

Molecular Mechanisms of Cartilage Repair and Their Possible Clinical Uses: A Review of Recent Developments

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