Composition of the pericellular matrix modulates the deformation behaviour of chondrocytes in articular cartilage under static loading

Chondrocyte hypertrophy is a characteristic of osteoarthritis and dominates bone growth. Intra-and extracellular changes that are known to be induced by metabolically active hypertrophic chondrocytes are known to contribute to hypertrophy. However, it is unknown to which extent these mechanical conditions together can be held responsible for the total magnitude of hypertrophy. The present paper aims to provide a quantitative, mechanically sound answer to that question. To address this aim requires a quantitative tool that captures the mechanical effects of collagen and proteoglycans, allows temporal changes in tissue composition, and can compute cell and tissue deformations. These requirements are met in our numerical model that is validated for articular cartilage mechanics, which we apply to quantitatively explain a range of experimental observations related to hypertrophy. After validating the numerical approach for studying hypertrophy, the model is applied to evaluate the direct mechanical effects of axial tension and compression on hypertrophy (Hueter-Volkmann principle) and to explore why hypertrophy is reduced in case of partially or fully compromised proteoglycan expression. Finally, a mechanical explanation is provided for the observation that chondrocytes do not hypertrophy when enzymatical collagen degradation is prohibited (S1Pcko knock-out mouse model). This paper shows that matrix turnover by metabolically active chondrocytes, together with externally applied mechanical conditions, can explain quantitatively the volumetric change of chondrocytes during hypertrophy. It provides a mechanistic explanation for the observation that collagen degradation results in chondrocyte hypertrophy, both under physiological and pathological conditions.

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“…These values are within the previously reported range (Julkunen et al 2009;Lai et al 2002;Likhitpanichkul et al 2005).…”

Section: Discussionsupporting

confidence: 92%

Mechanics of chondrocyte hypertrophy

Donkelaar

Wilson

2011

Biomech Model Mechanobiol

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“…In addition, direction-dependent material properties of the pericellular matrix can be prescribed, i.e. the region's fibre organization aligned tangentially to the chondrocyte surface [43] as a function of element centroid location relative to the chondrocyte. Finally, the loading and boundary conditions can be prescribed using deformation gradient and fluid pressure information (for biphasic case), e.g.…”

Section: Tissue -Cell Scale Model Developmentmentioning

confidence: 99%

Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

et al. 2015

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“…It is thought that this matrix plays a significant role in the deformation behaviour of chondrocytes, possibly modulating cartilage development, adaptation and degeneration (Julkunen et al 2009). The territorial matrix surrounds the pericellular matrix.…”

Section: Subregionsmentioning

confidence: 99%

Stem Cell Therapy for Cartilage Defects

Pastides

Khan

2015

Translational Medicine Research

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Cartilaginous defects within the articular cartilage present a treatment problem within the orthopaedic community. In cases of established osteoarthritis affecting large joints, arthroplasty is a good, well-established and predictable option. It is though a step too far for smaller and discrete lesions. Currently, surgical options include autologous chondrocyte implantation, microfracture, osteochondral autologous transplantation and even osteochondral allograft plugs. Tissue engineering techniques may prove to be the answer to this problem. There is plenty of interest in stem cell manipulation to induce chondrogenesis. The areas of research focus on the differentiation of multipotent mesenchymal stem cells but also more recently on the use of induced pluripotent stem cells. Furthermore, augmentation of repair can be facilitated by endogenous stimulants to these cells such as growth factors, gene therapy and scaffolds to maintain an optimum microenvironment. Endogenous stimulants aside, it does appear that exogenous methods of stimulation such as ultrasound and magnetic field applications can further augment and improve the reparative process. The aim of this chapter is to define the problem faced by the medical world due to the macro-and microscopic structure of cartilage and present data and reports showing the advances made in this field. The final section focuses on the current state of play surrounding the translation of these techniques to human subjects, presenting the up-to-date studies.

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Composition of the pericellular matrix modulates the deformation behaviour of chondrocytes in articular cartilage under static loading

Cited by 47 publications

References 52 publications

Mechanics of chondrocyte hypertrophy

Mechanics of chondrocyte hypertrophy

Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

Stem Cell Therapy for Cartilage Defects

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