Multiscale Strain Transfer in Cartilage

Boos, Manuela A; Lamandé, Shireen R.; Stok, Kathryn S.

doi:10.3389/fcell.2022.795522

Cited by 4 publications

(2 citation statements)

References 134 publications

(171 reference statements)

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“…Nevertheless, a huge challenge remains in the quantification of the relationship between the mechanical loads suffered by the knee joint and the resulting spatial variations of load magnitude and direction in the chondrocyte microenvironment. Therefore, a better characterization of the multi-scale stress transfer in KAC may support improved quantitative assessments of mechanoreceptor activations, to better understand the mechanisms of articular cartilage mechanobiology and remodelling (Boos et al, 2022).…”

Section: Figurementioning

confidence: 99%

Network-based modelling of mechano-inflammatory chondrocyte regulation in early osteoarthritis

Segarra-Queralt

Piella²,

Noailly³

2023

Front. Bioeng. Biotechnol.

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Osteoarthritis (OA) is a debilitating joint disease characterized by articular cartilage degradation, inflammation and pain. An extensive range of in vivo and in vitro studies evidences that mechanical loads induce changes in chondrocyte gene expression, through a process known as mechanotransduction. It involves cascades of complex molecular interactions that convert physical signals into cellular response(s) that favor either chondroprotection or cartilage destruction. Systematic representations of those interactions can positively inform early strategies for OA management, and dynamic modelling allows semi-quantitative representations of the steady states of complex biological system according to imposed initial conditions. Yet, mechanotransduction is rarely integrated. Hence, a novel mechano-sensitive network-based model is proposed, in the form of a continuous dynamical system: an interactome of a set of 118 nodes, i.e., mechano-sensitive cellular receptors, second messengers, transcription factors and proteins, related among each other through a specific topology of 358 directed edges is developed. Results show that under physio-osmotic initial conditions, an anabolic state is reached, whereas initial perturbations caused by pro-inflammatory and injurious mechanical loads leads to a catabolic profile of node expression. More specifically, healthy chondrocyte markers (Sox9 and CITED2) are fully expressed under physio-osmotic conditions, and reduced under inflammation, or injurious loadings. In contrast, NF-κB and Runx2, characteristic of an osteoarthritic chondrocyte, become activated under inflammation or excessive loading regimes. A literature-based evaluation shows that the model can replicate 94% of the experiments tested. Sensitivity analysis based on a factorial design of a treatment shows that inflammation has the strongest influence on chondrocyte metabolism, along with a significant deleterious effect of static compressive loads. At the same time, anti-inflammatory therapies appear as the most promising ones, though the restoration of structural protein production seems to remain a major challenge even in beneficial mechanical environments. The newly developed mechano-sensitive network model for chondrocyte activity reveals a unique potential to reflect load-induced chondroprotection or articular cartilage degradation in different mechano-chemical-environments.

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Section: Figurementioning

confidence: 99%

Network-based modelling of mechano-inflammatory chondrocyte regulation in early osteoarthritis

Segarra-Queralt

Piella²,

Noailly³

2023

Front. Bioeng. Biotechnol.

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“…Зокрема, критичні механічні власти-вості гіалінового хряща (пружність і жорсткість під час стискання) обумовлені можливістю агреканових комплексів пов'язувати воду [7]. Суглобовий хрящ поглинає навантаження через деформацію та забезпечує гладкість суглобових поверхонь для максимального зменшення тертя під час рухів у суглобі [8].…”

Section: результати та їх обговоренняunclassified

Conceptual model of the process of formation of immobilization contractures

Tyazhelov¹,

Khasawneh²,

Karpinska³

et al. 2023

OTP

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Contractures — limitation of passive movements in the joint — are a fairly frequent complication after immobilization or limitation of mobility and loading of the limb due to injuries, but the exact cause of their formation has not been clarified. Objective. Based on the meta-analysis of the results of experimental modeling and clinical studies of immobilization contractures, create a conceptual model of their formation. Methods. Literature sources from scientific bases were analyzed: Cochrane Library, Scopus, National Library of Medicine, ReLAB-HS Rehabilitation Resources Repository, Mendeley Reference Manager, The Physiological Society library, Google Scholar. Results. A conceptual model of the development of contractures was created. It is shown that immobilization of the joint of the injured limb blocks the execution of the signal of motor impulses. The lack of movement in the joint leads to a decrease in muscle strength and a slowdown in blood circulation. These processes are interrelated: hypotonia of the muscle is due to the restriction of nutrition through the blood supply, and the lack of contractile activity of the muscles leads to the rearrangement of the blood vessels. Articular cartilage is nourished through the subchondral bone and due to osmosis from the synovial fluid during movements. The lack of movement limits nutrition, protein synthesis is disrupted, the surface of the cartilage, synovial membrane and fluid begins to be rebuilt, the joint capsule, ligaments, and tendons thicken. At the same time, the structure of the muscles changes, they shorten and become denser. With long-term immobilization, degenerative processes in the tissues of the joint worsen its general condition, which can eventually lead to complete immobilization. Conclusions. The created conceptual model of the formation of immobilization contractures of joints takes into account the morphological changes of tissues as a result of immobilization. Immobilization affects all components of the joint and adjacent tissues from the first days, the changes progress over time. The use of the model will allow the development of a system of treatment measures to prevent the development of contractures.

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