Live free or die: Stretch-induced apoptosis occurs when adaptive reorientation of annulus fibrosus cells is restricted

Abbott, Rosalyn D.; Howe, Alan K.; Langevin, Hélène M.; Iatridis, James C.

doi:10.1016/j.bbrc.2012.04.018

Cited by 18 publications

(17 citation statements)

References 36 publications

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“…It was also observed that widespread remodeling of cytoskeletal components is primarily restricted to OAF cells in response to cyclic tensile strain, with increased F-actin turnover and increased β-actin, β-tubulin, and collagen I expression. Supporting these findings, experiments show that human AF cells reorient themselves perpendicular to the direction of applied uniaxial stretch in a fashion dependent on actin and focal adhesions, and undergo apoptosis if this reorientation is restricted using micropatterned membranes that define cell orientation under loading 156 .…”

Section: Af Cells Isolated From the Ecm Undergo Cell Morphology Changesmentioning

confidence: 71%

Mechanotransduction and cell biomechanics of the intervertebral disc

et al. 2018

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Mechanical loading of the intervertebral disc (IVD) initiates cell-mediated remodeling events that contribute to disc degeneration. Cells of the IVD, nucleus pulposus (NP) and anulus fibrosus (AF), will exhibit various responses to different mechanical stimuli which appear to be highly dependent on loading type, magnitude, duration, and anatomic zone of cell origin. Cells of the NP, the innermost region of the disc, exhibit an anabolic response to low-moderate magnitudes of static compression, osmotic pressure, or hydrostatic pressure, while higher magnitudes promote a catabolic response marked by increased protease expression and activity. Cells of the outer AF are responsive to physical forces in a manner that depends on frequency and magnitude, as are cells of the NP, though they experience different forces, deformations, pressure, and osmotic pressure in vivo. Much remains to be understood of the mechanotransduction pathways that regulate IVD cell responses to loading, including responses to specific stimuli and also differences among cell types. There is evidence that cytoskeletal remodeling and receptor-mediated signaling are important mechanotransduction events that can regulate downstream effects like gene expression and posttranslational biosynthesis, all of which may influence phenotype and bioactivity. These and other mechanotransduction events will be regulated by known and to-be-discovered cell-matrix and cell-cell interactions, and depend on composition of extracellular matrix ligands for cell interaction, matrix stiffness, and the phenotype of the cells themselves. Here, we present a review of the current knowledge of the role of mechanical stimuli and the impact upon the cellular response to loading and changes that occur with aging and degeneration of the IVD.

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Section: Af Cells Isolated From the Ecm Undergo Cell Morphology Changesmentioning

confidence: 71%

Mechanotransduction and cell biomechanics of the intervertebral disc

et al. 2018

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“…Injury to the AF leads to a number of pathological changes, including decreased IVD cellularity, upregulated matrix‐degrading enzymes, innervation, inflammation, increased growth factor production, and formation of granulation tissue . Delamination of the AF due to excessive loading increased apoptosis of outer annulocytes and it has been suggested that annulocyte apoptotic responses may be associated with excessive cell stretching of annulocytes with limited capacity to reorient and thereby minimize the strain from loading . Furthermore, aging of IVD tissues is known to induce aberrant cellular responses to injury, including cellular senescence and dysregulated signaling, and leads to the loss of biological structure and function, which may affect healing processes.…”

Section: Cellular Responses To Injurymentioning

confidence: 99%

“…3,100,101 Delamination of the AF due to excessive loading increased apoptosis of outer annulocytes and it has been suggested that annulocyte apoptotic responses may be associated with excessive cell stretching of annulocytes with limited capacity to reorient and thereby minimize the strain from loading. 102,103 Furthermore, aging of IVD tissues is known to induce aberrant cellular responses to injury, including cellular senescence and dysregulated signaling, and leads to the loss of biological structure and function, 104 which may affect healing processes. Young and old mice express similar patterns of anabolic cytokines, although differences in the degree of expression suggests different innate responsiveness as a function of age.…”

Section: Cellular Responses To Injurymentioning

confidence: 99%

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Torre

Mroz

Bartelstein

et al. 2018

Annals of the New York Academy of Sciences

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Despite considerable efforts to develop cellular, molecular, and structural repair strategies and restore intervertebral disk function after injury, the basic biology underlying intervertebral disk healing remains poorly understood. Remarkably, little is known about the origins of cell populations residing within the annulus fibrosus, or their phenotypes, heterogeneity, and roles during healing. This review focuses on recent literature highlighting the intrinsic and extrinsic cell types of the annulus fibrosus in the context of the injury and healing environment. Spatial, morphological, functional, and transcriptional signatures of annulus fibrosus cells are reviewed, including inner and outer annulus fibrosus cells, which we propose to be referred to as annulocytes. The annulus also contains peripheral cells, interlamellar cells, and potential resident stem/progenitor cells, as well as macrophages, T lymphocytes, and mast cells following injury. Phases of annulus fibrosus healing include inflammation and recruitment of immune cells, cell proliferation, granulation tissue formation, and matrix remodeling. However, annulus fibrosus healing commonly involves limited remodeling, with granulation tissues remaining, and the development of chronic inflammatory states. Identifying annulus fibrosus cell phenotypes during health, injury, and degeneration will inform reparative regeneration strategies aimed at improving annulus fibrosus healing.

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“…Previous studies have also demonstrated that the cytoskeleton might play a crucial role in mechanotransduction between IVD cells and their surrounding extracellular matrix [ 24 , 25 ]. As the F-actin cytoskeleton plays such a fundamental role in mechanotransduction between the extracellular matrix and IVD cells, it is likely that rearrangement of cytoskeletal networks may promote an imbalance in IVD homoeostasis, favoring a catabolic phenotype which is characteristic of degenerative disc disease [ 26 ]. More importantly, cytoskeleton rearrangement has been observed in discs from patients with low back pain or scoliosis compared to discs from healthy subjects [ 27 ].…”

Section: Resultsmentioning

confidence: 99%

Leptin Activates RhoA/ROCK Pathway to Induce Cytoskeleton Remodeling in Nucleus Pulposus Cells

Liang

et al. 2014

IJMS

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Hyperleptinemia is implicated in obesity-associated lumbar disc degeneration. Nevertheless, the effect of leptin on the intracellular signaling of nucleus pulposus cells is not clear. The current study sought to delineate the possible involvement of the RhoA/ROCK pathway in leptin-mediated cytoskeleton reorganization in nucleus pulposus cells. Nucleus pulposus cells isolated from scoliosis patients were treated with 10 ng/mL of leptin. Fluorescent resonance energy transfer analysis was used to determine the activation of RhoA signaling in nucleus pulposus cells. The protein expression of LIMK1 and cofilin-2 were analyzed by western blot analysis. F-actin cytoskeletal reorganization was assessed by rhodamine-conjugated phalloidin immunoprecipitation. Leptin induced F-actin reorganization and stress fiber formation in nucleus pulposus cells, accompanied by localized RhoA activation and phosphorylation of LIMK1 and cofilin. The RhoA inhibitor C3 exoenzyme or the ROCK inhibitor Y-27632 potently attenuated the effects of leptin on F-actin reorganization and stress fiber formation. Both inhibitors also prevented leptin-induced phosphorylation of LIMK1 and cofilin-2. Our study demonstrated that leptin activated the RhoA/ROCK/LIMK/cofilin-2 cascade to induce cytoskeleton reorganization in nucleus pulposus cells. These findings may provide novel insights into the pathogenic mechanism of obesity-associated lumbar disc degeneration.

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Live free or die: Stretch-induced apoptosis occurs when adaptive reorientation of annulus fibrosus cells is restricted

Cited by 18 publications

References 36 publications

Mechanotransduction and cell biomechanics of the intervertebral disc

Mechanotransduction and cell biomechanics of the intervertebral disc

Annulus fibrosus cell phenotypes in homeostasis and injury: implications for regenerative strategies

Leptin Activates RhoA/ROCK Pathway to Induce Cytoskeleton Remodeling in Nucleus Pulposus Cells

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