A mechanism underlying the movement requirement for synovial joint cavitation

Dowthwaite, Gary P.; Flannery, Carl R.; Flannelly, Joanne; Lewthwaite, J; Archer, Charles W.; Pitsillides, Andrew A.

doi:10.1016/s0945-053x(03)00037-4

Cited by 40 publications

(39 citation statements)

References 19 publications

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“…One other assumption made in this case was that the model would behave linearly. The magnitudes of strains on the models were comparable to those in published models and applied to in vitro cells 10,24 , with strains being below +3,500 and above -5,000 µɛ apart from constraint and muscle attachment points. Therefore, the strains at the relevant regions of the model were deemed within a range acceptable for a linear model.…”

Section: Discussionsupporting

confidence: 68%

Building Finite Element Models to Investigate Zebrafish Jaw Biomechanics

Brunt

Roddy

Rayfield

et al. 2016

JoVE

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Skeletal morphogenesis occurs through tightly regulated cell behaviors during development; many cell types alter their behavior in response to mechanical strain. Skeletal joints are subjected to dynamic mechanical loading. Finite element analysis (FEA) is a computational method, frequently used in engineering that can predict how a material or structure will respond to mechanical input. By dividing a whole system (in this case the zebrafish jaw skeleton) into a mesh of smaller 'finite elements', FEA can be used to calculate the mechanical response of the structure to external loads. The results can be visualized in many ways including as a 'heat map' showing the position of maximum and minimum principal strains (a positive principal strain indicates tension while a negative indicates compression. The maximum and minimum refer the largest and smallest strain). These can be used to identify which regions of the jaw and therefore which cells are likely to be under particularly high tensional or compressional loads during jaw movement and can therefore be used to identify relationships between mechanical strain and cell behavior. This protocol describes the steps to generate Finite Element models from confocal image data on the musculoskeletal system, using the zebrafish lower jaw as a practical example. The protocol leads the reader through a series of steps: 1) staining of the musculoskeletal components, 2) imaging the musculoskeletal components, 3) building a 3 dimensional (3D) surface, 4) generating a mesh of Finite Elements, 5) solving the FEA and finally 6) validating the results by comparison to real displacements seen in movements of the fish jaw.

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Section: Discussionsupporting

confidence: 68%

Building Finite Element Models to Investigate Zebrafish Jaw Biomechanics

Brunt

Roddy

Rayfield

et al. 2016

JoVE

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“…Molecular mechanisms responsible for transducing mechanical stimuli into changes in cell behavior remain unresolved in many tissues. A central role for ERK in the precise regulation of normal joint development, which requires mechanical input (57-61) and involves a local accumulation of HA-rich extracellular matrix, is, however, established (25,8,62,63). Our examination of p38 MAPK distribution in developing limbs revealed the presence of cells expressing constitutively active p38 MAPK at sites of joint cavity formation and is endorsed by our demonstration that cultured cells derived from these sites also conserve p38 MAPK in the active state.…”

Section: Discussionmentioning

confidence: 57%

A Specific Mechanomodulatory Role for p38 MAPK in Embryonic Joint Articular Surface Cell MEK-ERK Pathway Regulation

Lewthwaite

Bastow

Lamb

et al. 2006

Journal of Biological Chemistry

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Mechanisms regulating cell behavior and extracellular matrix composition in response to mechanical stimuli remain unresolved. Our previous studies have established that the MEK-ERK cascade plays a specific role in the mechano-dependent joint formation process by promoting the assembly of pericellular matrices reliant upon hyaluronan (HA) for their integrity. Here we demonstrate: (i) novel cross-talk between p38 MAPK and MEK-ERK signaling pathways that is specific for mechanical stimuli and (ii) a role for p38 MAPK in facilitating HA production by cells derived from the articular surface of embryonic chick tibiotarsal joints. We find that p38 MAPK blockade restricts pericellular assembly of HA-rich matrices and reduces basal as well as mechanical strain-induced release of HA. p38 MAPK blockers potentiated early strain-induced increases but restricted sustained increases in MEK/ERK phosphorylation at later times; c-Fos hyperphosphorylation at threonine 325 was found to parallel this p38 MAPK-mediated modulation of ERK activation. In contrast, p38 MAPK inhibitors had no detectable effect on the ERK activation induced by fibroblast growth factor 2 or pervanadate, a phosphatase inhibitor, and MEK inhibitors did not influence p38 MAPK phosphorylation, confirming both the specificity and unidirectionality of p38 MAPK-ERK cross-talk. Immunochemical and immunoblotting studies revealed constitutive p38 MAPK activation in cells at, or derived from, developing articular joint surfaces. Unlike the MEK-ERK pathway, however, p38 MAPK was not further stimulated by mechanical stimulation in vitro. Thus, p38 MAPK specifically facilitates ERK activation and downstream signaling in response to mechanical stimuli. These results suggest that constitutively active p38 MAPK serves an essential, permissive role in mechanically induced changes in ERK activation and in the accumulation of HA-rich extracellular matrices that serve a key role in joint development.Mitogen-activated protein kinases (MAPKs) 3 are ubiquitous serine/ threonine kinases that are activated by diverse extracellular stimuli, including growth factors, cytokines, and physiological mechanical signals (1-3). MAPKs are essential for transducing signals from the cell surface that regulate diverse cellular behaviors, such as those coordinating development, proliferation, and differentiation. Much recent emphasis has been placed on members of three well characterized mammalian MAPK families, comprising extracellular signal-regulated kinases (ERKs), p38 MAPKs, and c-Jun N-terminal kinases (JNKs) (4 -6). Until relatively recently it was considered that these families were preferentially activated by certain types of signal: the ERK family by growth factors and the p38 MAPK and JNK families by cellular stress. It is now becoming increasingly clear, however, that the various MAPK pathways can also be co-activated by a single stimulus. The precise interaction between members of these distinct MAPK families and how they cooperate to control cell behavior are, however, ill-define...

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“…Cyclic stretch was shown to augment hyaluronan production in human cervical fibroblasts [115]. CD44 levels and expression of mRNA for HAS3 were increased in strained fibrocartilage cells, highlighting the role for movement-induced stimuli in differential extracellular matrix metabolism during joint development, and showing that strain may differentially regulate HA synthase gene expression [116,117]. Cyclic compression of tendon explants resulted in synthesis and accumulation of large aggregating proteoglycans by resident fibroblasts, indicating an adaptive response in the development of fibrocartilage in locations where tendons are under compression [118,119].…”

Section: Role Of the Pericellular Matrix In Mechanotransduction And Cmentioning

confidence: 99%

Hyaluronan-dependent pericellular matrix☆

Evanko¹,

Tammi²,

Tammi³

et al. 2007

Advanced Drug Delivery Reviews

260

238

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Hyaluronan is a multifunctional glycosaminoglycan that forms the structural basis of the pericellular matrix. Hyaluronan is extruded directly through the plasma membrane by one of three hyaluronan synthases and anchored to the cell surface by the synthase or cell surface receptors such as CD44 or RHAMM. Aggregating proteoglycans and other hyaluronan-binding proteins, contribute to the material and biological properties of the matrix and regulate cell and tissue function. The pericellular matrix plays multiple complex roles in cell adhesion/de-adhesion, and cell shape changes associated with proliferation and locomotion. Time-lapse studies show that pericellular matrix formation facilitates cell detachment and mitotic cell rounding. Hyaluronan crosslinking occurs through various proteins, such as tenascin, TSG-6, inter-alpha-trypsin inhibitor, pentraxin and TSP-1. This creates higher order levels of structured hyaluronan that may regulate inflammation and other biological processes. Microvillous or filopodial membrane protrusions are created by active hyaluronan synthesis, and form the scaffold of hyaluronan coats in certain cells. The importance of the pericellular matrix in cellular mechanotransduction and the response to mechanical strain are also discussed.

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A mechanism underlying the movement requirement for synovial joint cavitation

Cited by 40 publications

References 19 publications

Building Finite Element Models to Investigate Zebrafish Jaw Biomechanics

Building Finite Element Models to Investigate Zebrafish Jaw Biomechanics

A Specific Mechanomodulatory Role for p38 MAPK in Embryonic Joint Articular Surface Cell MEK-ERK Pathway Regulation

Hyaluronan-dependent pericellular matrix☆

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