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Small oscillatory accelerations, independent of matrix deformations, increase osteoblast activity and enhance bone morphology.

Garman R, Rubin C, Judex S - PLoS ONE (2007)

Bottom Line: Oscillatory accelerations, applied in the absence of weight bearing, resulted in 70% greater bone formation rates in the trabeculae of the metaphysis, but similar levels of bone resorption, when compared to contralateral controls.Quantity and quality of trabecular bone also improved as a result of the acceleration stimulus, as evidenced by a significantly greater bone volume fraction (17%) and connectivity density (33%), and significantly smaller trabecular spacing (-6%) and structural model index (-11%).In retrospect, acceleration, as opposed to direct mechanical distortion, represents a more generic and safe, and perhaps more fundamental means of transducing physical challenges to the cells and tissues of an organism.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, United States of America.

ABSTRACT
A range of tissues have the capacity to adapt to mechanical challenges, an attribute presumed to be regulated through deformation of the cell and/or surrounding matrix. In contrast, it is shown here that extremely small oscillatory accelerations, applied as unconstrained motion and inducing negligible deformation, serve as an anabolic stimulus to osteoblasts in vivo. Habitual background loading was removed from the tibiae of 18 female adult mice by hindlimb-unloading. For 20 min/d, 5 d/wk, the left tibia of each mouse was subjected to oscillatory 0.6 g accelerations at 45 Hz while the right tibia served as control. Sham-loaded (n = 9) and normal age-matched control (n = 18) mice provided additional comparisons. Oscillatory accelerations, applied in the absence of weight bearing, resulted in 70% greater bone formation rates in the trabeculae of the metaphysis, but similar levels of bone resorption, when compared to contralateral controls. Quantity and quality of trabecular bone also improved as a result of the acceleration stimulus, as evidenced by a significantly greater bone volume fraction (17%) and connectivity density (33%), and significantly smaller trabecular spacing (-6%) and structural model index (-11%). These in vivo data indicate that mechanosensory elements of resident bone cell populations can perceive and respond to acceleratory signals, and point to an efficient means of introducing intense physical signals into a biologic system without putting the matrix at risk of overloading. In retrospect, acceleration, as opposed to direct mechanical distortion, represents a more generic and safe, and perhaps more fundamental means of transducing physical challenges to the cells and tissues of an organism.

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Osteocyte sitting in a lacuna within the matrix (left panel).The nucleus is coupled to the membrane by the cytoskeleton. Upon the application of large loads, the matrix strains and distorts the osteocyte (central panel). These large distortions result in the cytoskeleton pulling on the nucleus, and stimulating transcriptional activity. While this can stimulate a biologic response, it does so at risk of damaging the matrix. Upon the application of sinusoidal accelerations, the bone matrix moves forward and back (or up and down). The cell within the lacunae will oscillate out of phase with the matrix and the nucleus will oscillate out of phase with the cell body, causing the cytoskeleton to pull on the nucleus in the absence of matrix distortion (right panel). In this scenario, accelerations can alter biologic activity in the absence of direct loading, with the potential to distort the cell much greater than with direct loading of the calcified matrix.
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pone-0000653-g004: Osteocyte sitting in a lacuna within the matrix (left panel).The nucleus is coupled to the membrane by the cytoskeleton. Upon the application of large loads, the matrix strains and distorts the osteocyte (central panel). These large distortions result in the cytoskeleton pulling on the nucleus, and stimulating transcriptional activity. While this can stimulate a biologic response, it does so at risk of damaging the matrix. Upon the application of sinusoidal accelerations, the bone matrix moves forward and back (or up and down). The cell within the lacunae will oscillate out of phase with the matrix and the nucleus will oscillate out of phase with the cell body, causing the cytoskeleton to pull on the nucleus in the absence of matrix distortion (right panel). In this scenario, accelerations can alter biologic activity in the absence of direct loading, with the potential to distort the cell much greater than with direct loading of the calcified matrix.

Mentions: The mechanisms by which physical signals are sensed by a cell have routinely focused on specific components of the mechanical information resulting from load, such as stretch or shear of the cell membrane. The in vivo sensitivity of bone cells to even extremely small accelerations reported here suggests an alternative and efficient pathway for the transduction of physical signals to the transcriptional machinery of the nucleus (Fig. 4). Teleologically, accelerations represent a fundamentally efficient means of delivering regulatory physical information to the cell, and can be readily achieved even in the absence of matrix strains and large cellular deformations. Because the stiffness of the extracellular matrix across different tissues such as skin, ligament, or bone can differ by orders of magnitude, the ubiquitous nature of accelerations throughout the body could also provide a unifying principle by which adaptive cell systems are subject to, and respond to a given mechanical input (e.g., the transmission of a given deceleration on heel strike during locomotion would represent a generic signal to all tissues in the weightbearing musculoskeletal system). Of course, the well documented response of bone cells and tissue to large deformations in the virtual absence of significant accelerations (5–8 orders of magnitude lower than those employed here) [26], [27] emphasizes that there are a number of pathways by which cells can process physical input.


Small oscillatory accelerations, independent of matrix deformations, increase osteoblast activity and enhance bone morphology.

Garman R, Rubin C, Judex S - PLoS ONE (2007)

Osteocyte sitting in a lacuna within the matrix (left panel).The nucleus is coupled to the membrane by the cytoskeleton. Upon the application of large loads, the matrix strains and distorts the osteocyte (central panel). These large distortions result in the cytoskeleton pulling on the nucleus, and stimulating transcriptional activity. While this can stimulate a biologic response, it does so at risk of damaging the matrix. Upon the application of sinusoidal accelerations, the bone matrix moves forward and back (or up and down). The cell within the lacunae will oscillate out of phase with the matrix and the nucleus will oscillate out of phase with the cell body, causing the cytoskeleton to pull on the nucleus in the absence of matrix distortion (right panel). In this scenario, accelerations can alter biologic activity in the absence of direct loading, with the potential to distort the cell much greater than with direct loading of the calcified matrix.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC1919432&req=5

pone-0000653-g004: Osteocyte sitting in a lacuna within the matrix (left panel).The nucleus is coupled to the membrane by the cytoskeleton. Upon the application of large loads, the matrix strains and distorts the osteocyte (central panel). These large distortions result in the cytoskeleton pulling on the nucleus, and stimulating transcriptional activity. While this can stimulate a biologic response, it does so at risk of damaging the matrix. Upon the application of sinusoidal accelerations, the bone matrix moves forward and back (or up and down). The cell within the lacunae will oscillate out of phase with the matrix and the nucleus will oscillate out of phase with the cell body, causing the cytoskeleton to pull on the nucleus in the absence of matrix distortion (right panel). In this scenario, accelerations can alter biologic activity in the absence of direct loading, with the potential to distort the cell much greater than with direct loading of the calcified matrix.
Mentions: The mechanisms by which physical signals are sensed by a cell have routinely focused on specific components of the mechanical information resulting from load, such as stretch or shear of the cell membrane. The in vivo sensitivity of bone cells to even extremely small accelerations reported here suggests an alternative and efficient pathway for the transduction of physical signals to the transcriptional machinery of the nucleus (Fig. 4). Teleologically, accelerations represent a fundamentally efficient means of delivering regulatory physical information to the cell, and can be readily achieved even in the absence of matrix strains and large cellular deformations. Because the stiffness of the extracellular matrix across different tissues such as skin, ligament, or bone can differ by orders of magnitude, the ubiquitous nature of accelerations throughout the body could also provide a unifying principle by which adaptive cell systems are subject to, and respond to a given mechanical input (e.g., the transmission of a given deceleration on heel strike during locomotion would represent a generic signal to all tissues in the weightbearing musculoskeletal system). Of course, the well documented response of bone cells and tissue to large deformations in the virtual absence of significant accelerations (5–8 orders of magnitude lower than those employed here) [26], [27] emphasizes that there are a number of pathways by which cells can process physical input.

Bottom Line: Oscillatory accelerations, applied in the absence of weight bearing, resulted in 70% greater bone formation rates in the trabeculae of the metaphysis, but similar levels of bone resorption, when compared to contralateral controls.Quantity and quality of trabecular bone also improved as a result of the acceleration stimulus, as evidenced by a significantly greater bone volume fraction (17%) and connectivity density (33%), and significantly smaller trabecular spacing (-6%) and structural model index (-11%).In retrospect, acceleration, as opposed to direct mechanical distortion, represents a more generic and safe, and perhaps more fundamental means of transducing physical challenges to the cells and tissues of an organism.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Engineering, State University of New York at Stony Brook, Stony Brook, New York, United States of America.

ABSTRACT
A range of tissues have the capacity to adapt to mechanical challenges, an attribute presumed to be regulated through deformation of the cell and/or surrounding matrix. In contrast, it is shown here that extremely small oscillatory accelerations, applied as unconstrained motion and inducing negligible deformation, serve as an anabolic stimulus to osteoblasts in vivo. Habitual background loading was removed from the tibiae of 18 female adult mice by hindlimb-unloading. For 20 min/d, 5 d/wk, the left tibia of each mouse was subjected to oscillatory 0.6 g accelerations at 45 Hz while the right tibia served as control. Sham-loaded (n = 9) and normal age-matched control (n = 18) mice provided additional comparisons. Oscillatory accelerations, applied in the absence of weight bearing, resulted in 70% greater bone formation rates in the trabeculae of the metaphysis, but similar levels of bone resorption, when compared to contralateral controls. Quantity and quality of trabecular bone also improved as a result of the acceleration stimulus, as evidenced by a significantly greater bone volume fraction (17%) and connectivity density (33%), and significantly smaller trabecular spacing (-6%) and structural model index (-11%). These in vivo data indicate that mechanosensory elements of resident bone cell populations can perceive and respond to acceleratory signals, and point to an efficient means of introducing intense physical signals into a biologic system without putting the matrix at risk of overloading. In retrospect, acceleration, as opposed to direct mechanical distortion, represents a more generic and safe, and perhaps more fundamental means of transducing physical challenges to the cells and tissues of an organism.

Show MeSH
Related in: MedlinePlus