Depth and strain rate-dependent mechanical response of chondrocytes in reserve zone cartilage subjected to compressive loading

Kazemi, Masumeh; Williams, John L.

doi:10.1007/s10237-021-01457-1

Cited by 7 publications

(4 citation statements)

References 69 publications

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“…We employed a single phase, isotropic, elastic model to avoid the complexity of the multiphase, anisotropic, and non-homogeneous properties since those have not been determined for RZ cartilage in the growth plate and are not well characterized for the proliferative and hypertrophic layers. While representing cartilage as a single-phase material is a significant approximation of cartilage behavior, we argue that it can serve as a reasonable approximation of either the long-time equilibrium response [37] or the shorttime behavior [5]. Based on comparisons between a multiscale poroelastic model at high strain rates [5] and an elastic model of cells embedded within the growth plate RZ [3], we believe that a single-phase elastic model provides insight into the mechanical environment within the growth plate for loading at high strain rates during short time intervals such as during initial foot and ground contact in gait or running.…”

Section: Discussionmentioning

confidence: 96%

“…Growth plate chondrocytes moderate bone growth in response to mechanical loads by transducing strains and stresses into intracellular biochemical signals through a variety of mechanisms under active investigation. Computational models of cells in the proliferative zone (PZ), hypertrophic zone (HZ), and reserve zone (RZ) have revealed depth-and zone-dependent variations in cellular stress and strain [1,2,3,4,5]. Computational modeling has also shown that the RZ chondrocyte pericellular matrix (PCM) is an essential component of the cell's mechanosensory mechanism [3].…”

Section: Introductionmentioning

confidence: 99%

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Primary Chondrocyte Cilium Strains Increase with Depth Within the Growth Plate Reserve Zone and Reflect Loading Direction Across the Growth Plate

Carrion¹,

Williams²

2022

Mechanobiol J

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Background. It is known that reserve zone (RZ) chondrocytes regulate the organization of the physis and that chondrocyte primary cilia (PC) act as mechanotransducers. Objective. To explore if physeal loading-induced strains in RZ chondrocyte PC can enable cells to sense whether the physis is subjected to increasing or decreasing levels of compression. Methods. Finite element models of RZ chondrocytes within the physis were created to examine strains developed in the PC when the physis is subjected to either 10% compression or tension. The PC were oriented either toward the epiphysis or metaphysis. Findings. PC basal body axial and transverse strains were negative when the physis was compressed and positive when subjected to tension. Axial strains in the cilium body transition zone also followed the applied loading and were amplified up to 4X, whereas membrane strains transverse to the cilium were tensile under physeal compression, possibly stretching integrin receptors. Tension applied to the physis stretched the cilium membrane in the axial direction. Conclusion. PC perceive strains in ways that may explain the regulatory function of RZ chondrocytes and their role in modulating bone growth.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Primary Chondrocyte Cilium Strains Increase with Depth Within the Growth Plate Reserve Zone and Reflect Loading Direction Across the Growth Plate

Carrion¹,

Williams²

2022

Mechanobiol J

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“…Stretch of chondrocytes in 2D aims to model the pericellular ECM deformations, 127 tensile strains, 60,61 and cell shape changes [127][128][129][130][131][132][133] that occur during 3D compression of cartilage matrix and embedded cells. While there are limitations and assumptions, 2D stretch has been employed to investigate chondrocyte mechanobiology.…”

Section: Discussionmentioning

confidence: 99%

A high throughput cell stretch device for investigating mechanobiology in vitro

Pratt,

Plunkett,

Kuzu

et al. 2024

APL Bioengineering

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Mechanobiology is a rapidly advancing field, with growing evidence that mechanical signaling plays key roles in health and disease. To accelerate mechanobiology-based drug discovery, novel in vitro systems are needed that enable mechanical perturbation of cells in a format amenable to high throughput screening. Here, both a mechanical stretch device and 192-well silicone flexible linear stretch plate were designed and fabricated to meet high throughput technology needs for cell stretch-based applications. To demonstrate the utility of the stretch plate in automation and screening, cell dispensing, liquid handling, high content imaging, and high throughput sequencing platforms were employed. Using this system, an assay was developed as a biological validation and proof-of-concept readout for screening. A mechano-transcriptional stretch response was characterized using focused gene expression profiling measured by RNA-mediated oligonucleotide Annealing, Selection, and Ligation with Next-Gen sequencing. Using articular chondrocytes, a gene expression signature containing stretch responsive genes relevant to cartilage homeostasis and disease was identified. The possibility for integration of other stretch sensitive cell types (e.g., cardiovascular, airway, bladder, gut, and musculoskeletal), in combination with alternative phenotypic readouts (e.g., protein expression, proliferation, or spatial alignment), broadens the scope of high throughput stretch and allows for wider adoption by the research community. This high throughput mechanical stress device fills an unmet need in phenotypic screening technology to support drug discovery in mechanobiology-based disease areas.

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“…The information points to a possible connection between the pathophysiology and development of OA and the exposure of chondrocytes and cartilage to aberrant mechanical loading ( Zhu et al, 2010 ). Another study measured the FSS in the interstices surrounding the chondrocytes in growth plate cartilage, demonstrating that the FSS, which is caused by fluid flow over the cell surface, may have the ability to stimulate chondrocytes in the reserve zone close to the subchondral bone plate interface ( Kazemi and Williams, 2021 ).…”

Section: Classification and The Influence Of Mechanical Stimulimentioning

confidence: 99%

Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering

Jia,

Le,

Wang

et al. 2023

Front. Bioeng. Biotechnol.

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Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.

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Depth and strain rate-dependent mechanical response of chondrocytes in reserve zone cartilage subjected to compressive loading

Cited by 7 publications

References 69 publications

Primary Chondrocyte Cilium Strains Increase with Depth Within the Growth Plate Reserve Zone and Reflect Loading Direction Across the Growth Plate

Primary Chondrocyte Cilium Strains Increase with Depth Within the Growth Plate Reserve Zone and Reflect Loading Direction Across the Growth Plate

A high throughput cell stretch device for investigating mechanobiology in vitro

Double-edged role of mechanical stimuli and underlying mechanisms in cartilage tissue engineering

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