Chondrocyte cells respond mechanically to compressive loads

Freeman, P. M.; Natarajan, Raghu N.; Kimura, James H.; Andriacchi, T.P.

doi:10.1002/jor.1100120303

Cited by 171 publications

(109 citation statements)

References 14 publications

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“…Such modifications in the cytoskeleton are believed to be involved in the activation of ion channels and intracellular calcium signalling [47]. Compression might also reduce the cell volume, due to cellular confinement and the increase in extracellular osmolality [26].…”

Section: Direct Stimulusmentioning

confidence: 99%

The effects of dynamic loading on the intervertebral disc

2011

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Loading is important to maintain the balance of matrix turnover in the intervertebral disc (IVD). Daily cyclic diurnal assists in the transport of large soluble factors across the IVD and its surrounding circulation and applies direct and indirect stimulus to disc cells. Acute mechanical injury and accumulated overloading, however, could induce disc degeneration. Recently, there is more information available on how cyclic loading, especially axial compression and hydrostatic pressure, affects IVD cell biology. This review summarises recent studies on the response of the IVD and stem cells to applied cyclic compression and hydrostatic pressure. These studies investigate the possible role of loading in the initiation and progression of disc degeneration as well as quantifying a physiological loading condition for the study of disc degeneration biological therapy. Subsequently, a possible physiological/beneficial loading range is proposed. This physiological/beneficial loading could provide insight into how to design loading regimes in specific system for the testing of various biological therapies such as cell therapy, chemical therapy or tissue engineering constructs to achieve a better final outcome. In addition, the parameter space of 'physiological' loading may also be an important factor for the differentiation of stem cells towards most ideally 'discogenic' cells for tissue engineering purpose.

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Section: Direct Stimulusmentioning

confidence: 99%

The effects of dynamic loading on the intervertebral disc

2011

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“…The equilibrium response ( t → ∞) for either loading profile is the same according to (23) and (32), obeying σ z (∞)= E Y ε z (∞). Experimentally, Young's modulus of chondrocytes has been determined from either micropipette aspiration Jones et al 1999), unconfined compression (Leipzig and Athanasiou 2005), indentation with atomic force microscopy (Hung et al 2001), or compression of cell-seeded agarose constructs (Freeman et al 1994), yielding consistent results where E Y is on the order of 1 kPa.…”

Section: Analysis Of Responsementioning

confidence: 99%

A Theoretical Analysis of Water Transport Through Chondrocytes

Ateshian

Costa

Hung

2006

Biomech Model Mechanobiol

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Because of the avascular nature of adult cartilage nutrients and waste products are transported to and from the chondrocytes by diffusion and convection through the extracellular matrix. The convective interstitial fluid flow within and around chondrocytes is poorly understood. This theoretical study demonstrates that the incorporation of a semi-permeable membrane when modeling the chondrocyte leads to the following findings: Under mechanical loading of an isolated chondrocyte the intracellular fluid pressure is on the order of tens of Pascals and the transmembrane fluid outflow, on the order of picometers per second, takes several days to subside; consequently the chondrocyte behaves practically as an incompressible solid whenever the loading duration is on the order of minutes or hours. When embedded in its extracellular matrix, the chondrocyte response is substantially different. Mechanical loading of the tissue leads to a fluid pressure difference between intracellular and extracellular compartments on the order of tens of kilopascals and the transmembrane outflow, on the order of a nanometer per second, subsides in about one hour. The volume of the chondrocyte decreases concomitantly with that of the extracellular matrix. The interstitial fluid flow in the extracellular matrix is directed around the cell, with peak values on the order of tens of nanometers per second. The viscous fluid shear stress acting on the cell surface is orders of magnitude smaller than the solid matrix shear stresses resulting from the extracellular matrix deformation. These results provide new insight toward our understanding of water transport in chondrocytes.

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“…The relatively simple case of a ramp-and-hold static compression of cartilage can result in transient interstitial fluid expression, cell deformation (25), increased osmolarity (26), decreased extracellular pH (27), changes in fixed charge density (28), and altered transport of soluble factors within the tissue (22). Each of these physical phenomena may potentially act as a "mechano-ligand" activating or inhibiting one or more signaling pathways.…”

mentioning

confidence: 99%

Mechanical Regulation of Mitogen-activated Protein Kinase Signaling in Articular Cartilage

Fanning

Emkey

Smith

et al. 2003

Journal of Biological Chemistry

118

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Articular chondrocytes respond to mechanical forces by alterations in gene expression, proliferative status, and metabolic functions. Little is known concerning the cell signaling systems that receive, transduce, and convey mechanical information to the chondrocyte interior. Here, we show that ex vivo cartilage compression stimulates the phosphorylation of ERK1/2, p38 MAPK, and SAPK/ERK kinase-1 (SEK1) of the JNK pathway. Mechanical compression induced a phased phosphorylation of ERK consisting of a rapid induction of ERK1/2 phosphorylation at 10 min, a rapid decay, and a sustained level of ERK2 phosphorylation that persisted for at least 24 h. Mechanical compression also induced the phosphorylation of p38 MAPK in strictly a transient fashion, with maximal phosphorylation occurring at 10 min. Mechanical compression stimulated SEK1 phosphorylation, with a maximum at the relatively delayed time point of 1 h and with a higher amplitude than ERK1/2 and p38 MAPK phosphorylation. These data demonstrate that mechanical compression alone activates MAPK signaling in intact cartilage. In addition, these data demonstrate distinct temporal patterns of MAPK signaling in response to mechanical loading and to the anabolic insulin-like growth factor-I. Finally, the data indicate that compression coactivates distinct signaling pathways that may help define the nature of mechanotransduction in cartilage.

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Chondrocyte cells respond mechanically to compressive loads

Cited by 171 publications

References 14 publications

The effects of dynamic loading on the intervertebral disc

The effects of dynamic loading on the intervertebral disc

A Theoretical Analysis of Water Transport Through Chondrocytes

Mechanical Regulation of Mitogen-activated Protein Kinase Signaling in Articular Cartilage

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