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Mechanical Stimuli (mechanical + stimulus)
Selected AbstractsPrevention of Postmenopausal Bone Loss by a Low-Magnitude, High-Frequency Mechanical Stimuli: A Clinical Trial Assessing Compliance, Efficacy, and Safety,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Clinton Rubin Abstract A 1-year prospective, randomized, double-blind, and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low-level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass. Introduction: Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low-magnitude vibration (<0.3g), applied at a relatively high frequency (20,90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1-year prospective, randomized, double-blind, and placebo-controlled clinical trial in 70 women, 3,8 years past the menopause, examined the ability of such high-frequency, low-magnitude mechanical signals to inhibit bone loss in the human. Materials and Methods: Each day, one-half of the subjects were exposed to short-duration (two 10-minute treatments/day), low-magnitude (2.0 m/s2 peak to peak), 30-Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty-six women completed the 1-year treatment. Results and Conclusions: The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention. [source] Human Bone Cell Hyperpolarization Response to Cyclical Mechanical Strain Is Mediated by an Interleukin-1, Autocrine/Paracrine LoopJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2000D. M. Salter Abstract Mechanical stimuli imparted by stretch, pressure, tension, fluid flow, and shear stress result in a variety of biochemical responses important in bone (re)modeling. The molecules involved in the recognition and transduction of mechanical stimuli that lead to modulation of bone cell function are not yet fully characterized. Cyclical pressure-induced strain (PIS) induces a rapid change in membrane potential of human bone cells (HBC) because of opening of membrane ion channels. This response is mediated via integrins and requires tyrosine kinase activity and an intact actin cytoskeleton. We have used this electrophysiological response to further study the signaling events occurring early after mechanical stimulation of HBC. Stimulation of HBC at 0.33Hz PIS, but not 0.104 Hz PIS, results in the production of a transferable factor that induces membrane hyperpolarization of unstimulated HBC. The production of this factor is inhibited by antibodies to ,1-integrin. Interleukin-1, (IL-1,) and prostaglandin E2 (PGE2) were identified as candidate molecules for the transferable factor as both were shown to induce HBC hyperpolarization by opening of small conductance calcium-activated potassium channels, the means by which 0.33 Hz PIS causes HBC hyperpolarization. Antibodies to IL-1,, but not other cytokines studied, inhibit the hyperpolarization response of HBC to 0.33 Hz PIS. Comparison of the signaling pathways required for 0.33 Hz PIS and IL-1,-induced membrane hyperpolarization shows that both involve the phospholipase C/inositol triphosphate pathway, protein kinase C (PKC), and prostaglandin synthesis. Unlike 0.33 Hz PIS-induced membrane hyperpolarization, IL-1,-induced hyperpolarization does not require tyrosine kinase activity or an intact actin cytoskeleton. These studies suggest that 0.33 Hz PIS of HBC induces a rapid, integrin-mediated, release of IL-1, with a subsequent autocrine/paracrine loop resulting in membrane hyperpolarization. IL-1, production in response to mechanical stimuli is potentially of importance in regulation of bone (re)modeling. [source] Actin stress fiber pre-extension in human aortic endothelial cellsCYTOSKELETON, Issue 4 2008Lan Lu Abstract Actin stress fibers (SFs) enable cells to sense and respond to mechanical stimuli and affect adhesion, motility and apoptosis. We and others have demonstrated that cultured human aortic endothelial cells (HAECs) are internally stressed so that SFs are pre-extended beyond their unloaded lengths. The present study explores factors affecting SF pre-extension. In HAECs cultured overnight the baseline pre-extension was 1.10 and independent of the amount of cell shortening. Decreasing contractility with 30 mM BDM or 10 ,M blebbistatin decreased pre-extension to 1.05 whereas increasing contractility with 2 nM calyculin A increased pre-extension to 1.26. Knockdown of ,-actinin-1 with an interfering RNA increased pre-extension to 1.28. None of these affected the wavelength of the buckled SFs. Pre-extension was the same in unperturbed cells as in those in which the actin cytoskeleton was disrupted by both chemical and mechanical means and then allowed to reassemble. Finally, disrupting MTs or IFs did not affect pre-extension but increased the wavelength. Taken together, these results suggest that pre-extension of SFs is determined primarily by intrinsic factors, i.e. the level of actin-myosin interaction. This intrinsic control of pre-extension is sufficiently robust that pre-extension is the same even after the actin cytoskeleton has been disrupted and reorganized. Unlike pre-extension, the morphology of the compressed SFs is partially determined by MTs and IFs which appear to support the SFs along their lengths. Cell Motil. Cytoskeleton 2008. © 2008 Wiley-Liss, Inc. [source] Effects of plant and prey characteristics on the predatory behavior of Delphastus catalinaeENTOMOLOGIA EXPERIMENTALIS ET APPLICATA, Issue 1 2006Moshe Guershon Abstract Nymphal setosity of the whitefly Bemisia tabaci Gennadius (Homoptera: Aleyrodidae) has been reported to be induced by mechanical stimuli such as leaf tomentosity, and related to the predatory performance of the coccinellid Delphastus catalinae (Horn) (Coleoptera: Coccinellidae). In this study, a possible adaptive value of this phenomenon for the whitefly is shown through the combined effects of leaf and prey characteristics on the walking and predatory behaviors of the beetle. Leaf tomentosity significantly affected the walking patterns of the beetle and therefore its searching abilities, thus indirectly increasing the influence of prey distribution upon predator's efficiency. Moreover, while searching on tomentose leaves, the beetles showed preference for the smooth prey phenotype. This behavior was found dependent on the experience of the beetle in previous encounters. These results are pertinent to intraspecific competition between the different nymphal phenotypes and to the predatory efficiency of this beetle, which is utilized in biological control of whiteflies. [source] Fatty acid metabolism assessed by 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) and expression of fatty acid utilization enzymes in volume-overloaded heartsEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 3 2004T. Miyamoto Abstract Background, The peroxisome proliferator-activated receptor (PPAR) , is a member of the nuclear receptor superfamily and regulates gene expression of fatty acid utilization enzymes. In cardiac hypertrophy and heart failure by pressure-overload, myocardial energy utilization reverts to the fetal pattern, and metabolic substrate switches from fatty acid to glucose. However, myocardial metabolism in volume-overloaded hearts has not been rigorously studied. The aim of the present study was to examine fatty acid metabolism and protein expressions of PPAR, and fatty acid oxidation enzymes in volume-overloaded rabbit hearts. Methods, Volume-overload was induced by carotid-jugular shunt formation. Sham-operated rabbits were used as control. Chronic volume-overload increased left ventricular weight and ventricular cavity size, and relative wall thickness was decreased, indicating eccentric cardiac hypertrophy. 125I-iodophenyl 9-methylpentadecanoic acid (9MPA) was intravenously administered, and animals were sacrificed at 5 min after injection. The 9MPA was rapidly metabolized to iodophenyl-3-methylnonanoic acid (3MNA) by ,-oxidation. Lipid extraction from the myocardium was performed by the Folch method, and radioactivity distribution of metabolites was assayed by thin-layer chromatography. The protein was extracted from the left ventricular myocardium, and levels of PPAR, and fatty acid oxidation enzymes were examined by Western blotting. Results, Myocardial distribution of 9MPA tended to be more heterogeneous in shunt than in sham rabbits (P = 0·06). In volume-overloaded hearts by shunt, the conversion from 9MPA to 3MNA by ,-oxidation was faster than the sham-control hearts (P < 0·05). However, protein levels of PPAR, and fatty acid utilization enzymes were unchanged in shunt rabbits compared with sham rabbits. Conclusions, These data suggest that myocardial fatty acid metabolism is enhanced in eccentric cardiac hypertrophy by volume-overload without changes in protein expressions of PPAR, and fatty acid utilization enzymes. Our data may provide a novel insight into the subcellular mechanisms for the pathological process of cardiac remodelling in response to mechanical stimuli. [source] Differences in Local Environment Determine the Site of Physiological Angiogenesis in Rat Skeletal MuscleEXPERIMENTAL PHYSIOLOGY, Issue 5 2003I. Badr The specificity in location of angiogenesis to either glycolytic or oxidative fibre types, or muscle regions, was examined in the tibialis anterior (TA) and extensor digitorum longus (EDL) muscles of rat. Angiogenesis was induced by mechanical means either with (chronic muscle stimulation) or without (muscle stretch by overload) changes in blood flow, treatments which invoked only minor changes in fibre type and fibre size. Proliferation estimated by PCNA labelling of cells co-localised with capillaries was very rare in control muscles, where it occurred mainly in the glycolytic regions, but was increased in both models of angiogenesis. However, when labelled capillaries were scored according to the type of surrounding fibres, only muscle stimulation significantly accentuated proliferation of capillaries surrounded by glycolytic fibres. We conclude that while mechanical stimuli are important for proliferation in glycolytic regions in both models, capillary growth occurs specifically around glycolytic fibres in that region when the angiogenic stimulus includes increased blood flow and/or increased metabolic demand. [source] Involvement of the cytoskeletal elements in articular cartilage homeostasis and pathologyINTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 1 2009Emma J. Blain Summary The cytoskeleton of all cells is a three-dimensional network comprising actin microfilaments, tubulin microtubules and intermediate filaments. Studies in many cell types have indicated roles for these cytoskeletal proteins in many diverse cellular processes including alteration of cell shape, movement of organelles, migration, endocytosis, secretion, cell division and extracellular matrix assembly. The cytoskeletal networks are highly organized in structure enabling them to fulfil their biological functions. This review will primarily focus on the organization and function of the three major cytoskeletal networks in articular cartilage chondrocytes. Articular cartilage is a major load-bearing tissue of the synovial joint; it is well known that the cytoskeleton acts as a physical interface between the chondrocytes and the extracellular matrix in ,sensing' mechanical stimuli. The effect of mechanical load on cytoskeletal element expression and organization will also be reviewed. Abnormal mechanical load is widely believed to be a risk factor for the development of osteoarthritis. Several studies have intimated that the major cytoskeletal networks are disorganized or often absent in osteoarthritic cartilage chondrocytes. The implications and possible reasoning for this are more widely discussed and placed into context with their potential relevance to disease and therapeutic strategies. [source] Effects of Aging on Hand FunctionJOURNAL OF AMERICAN GERIATRICS SOCIETY, Issue 11 2001Vinoth K. Ranganathan MSE OBJECTIVES: The purpose of this study was to quantify age-induced changes in handgrip and finger-pinch strength, ability to maintain a steady submaximal finger pinch force and pinch posture, speed in relocating small objects with finger grip, and ability to discriminate two identical mechanical stimuli applied to the finger tip. DESIGN: A cross-sectional study. SETTINGS: Greater Cleveland area of Ohio. PARTICIPANTS: Healthy, independent, young (n = 27, range 20,35 years) and older (n = 28, range 65,79 years) subjects. MEASUREMENTS: Handgrip strength, maximum pinch force (MPF), ability to maintain a steady pinch force at three relative force levels (5%, 10%, and 20% MPF) and three absolute force levels (2.5 Newtons (N), 4 N, and 8 N), ability to maintain a precision pinch posture, speed in relocating pegs from a nearby location onto the pegboard, and the shortest distance for discriminating two stimuli were measured in both young and older groups. RESULTS: Compared with young subjects, the older group's handgrip force was 30% weaker (P < .001), MPF was 26% lower (P < .05), and ability to maintain steady submaximal pinch force and a precision pinch posture was significantly less (P < .05). The time taken to relocate the pegs and the distance needed to discriminate two identical stimuli increased significantly with age (P < .01). The decrease in the ability to maintain steady submaximal pinch force was more pronounced in women than men. CONCLUSION: Aging has a degenerative effect on hand function, including declines in hand and finger strength and ability to control submaximal pinch force and maintain a steady precision pinch posture, manual speed, and hand sensation. [source] Aged mice have enhanced endocortical response and normal periosteal response compared with young-adult mice following 1 week of axial tibial compressionJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2010Michael D Brodt Abstract With aging, the skeleton may lose its ability to respond to positive mechanical stimuli. We hypothesized that aged mice are less responsive to loading than young-adult mice. We subjected aged (22 months) and young-adult (7 months) BALB/c male mice to daily bouts of axial tibial compression for 1 week and evaluated cortical and trabecular responses using micro,computed tomography (µCT) and dynamic histomorphometry. The right legs of 95 mice were loaded for 60 rest-inserted cycles per day to 8, 10, or 12,N peak force (generating mid-diaphyseal strains of 900 to 1900 µ, endocortically and 1400 to 3100 µ, periosteally). At the mid-diaphysis, mice from both age groups showed a strong anabolic response on the endocortex (Ec) and periosteum (Ps) [Ec.MS/BS and Ps. MS/BS: loaded (right) versus control (left), p,<,.05]. Generally, bone formation increased with increasing peak force. At the endocortical surface, contrary to our hypothesis, aged mice had a significantly greater response to loading than young-adult mice (Ec.MS/BS and Ec.BFR/BS: 22 months versus 7 months, p,<,.001). Responses at the periosteal surface did not differ between age groups (p,>,.05). The loading-induced increase in bone formation resulted in increased cortical area in both age groups (loaded versus control, p,<,.05). In contrast to the strong cortical response, loading only weakly stimulated trabecular bone formation. Serial (in vivo) µCT examinations at the proximal metaphysis revealed that loading caused a loss of trabecular bone in 7-month-old mice, whereas it appeared to prevent bone loss in 22-month-old mice. In summary, 1 week of daily tibial compression stimulated a robust endocortical and periosteal bone-formation response at the mid-diaphysis in both young-adult and aged male BALB/c mice. We conclude that aging does not limit the short-term anabolic response of cortical bone to mechanical stimulation in our animal model. © 2010 American Society for Bone and Mineral Research [source] Prevention of Postmenopausal Bone Loss by a Low-Magnitude, High-Frequency Mechanical Stimuli: A Clinical Trial Assessing Compliance, Efficacy, and Safety,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 3 2004Clinton Rubin Abstract A 1-year prospective, randomized, double-blind, and placebo-controlled trial of 70 postmenopausal women demonstrated that brief periods (<20 minutes) of a low-level (0.2g, 30 Hz) vibration applied during quiet standing can effectively inhibit bone loss in the spine and femur, with efficacy increasing significantly with greater compliance, particularly in those subjects with lower body mass. Introduction: Indicative of the anabolic potential of mechanical stimuli, animal models have demonstrated that short periods (<30 minutes) of low-magnitude vibration (<0.3g), applied at a relatively high frequency (20,90 Hz), will increase the number and width of trabeculae, as well as enhance stiffness and strength of cancellous bone. Here, a 1-year prospective, randomized, double-blind, and placebo-controlled clinical trial in 70 women, 3,8 years past the menopause, examined the ability of such high-frequency, low-magnitude mechanical signals to inhibit bone loss in the human. Materials and Methods: Each day, one-half of the subjects were exposed to short-duration (two 10-minute treatments/day), low-magnitude (2.0 m/s2 peak to peak), 30-Hz vertical accelerations (vibration), whereas the other half stood for the same duration on placebo devices. DXA was used to measure BMD at the spine, hip, and distal radius at baseline, and 3, 6, and 12 months. Fifty-six women completed the 1-year treatment. Results and Conclusions: The detection threshold of the study design failed to show any changes in bone density using an intention-to-treat analysis for either the placebo or treatment group. Regression analysis on the a priori study group demonstrated a significant effect of compliance on efficacy of the intervention, particularly at the lumbar spine (p = 0.004). Posthoc testing was used to assist in identifying various subgroups that may have benefited from this treatment modality. Evaluating those in the highest quartile of compliance (86% compliant), placebo subjects lost 2.13% in the femoral neck over 1 year, whereas treatment was associated with a gain of 0.04%, reflecting a 2.17% relative benefit of treatment (p = 0.06). In the spine, the 1.6% decrease observed over 1 year in the placebo group was reduced to a 0.10% loss in the active group, indicating a 1.5% relative benefit of treatment (p = 0.09). Considering the interdependence of weight, the spine of lighter women (<65 kg), who were in the highest quartile of compliance, exhibited a relative benefit of active treatment of 3.35% greater BMD over 1 year (p = 0.009); for the mean compliance group, a 2.73% relative benefit in BMD was found (p = 0.02). These preliminary results indicate the potential for a noninvasive, mechanically mediated intervention for osteoporosis. This non-pharmacologic approach represents a physiologically based means of inhibiting the decline in BMD that follows menopause, perhaps most effectively in the spine of lighter women who are in the greatest need of intervention. [source] Quantity and Quality of Trabecular Bone in the Femur Are Enhanced by a Strongly Anabolic, Noninvasive Mechanical InterventionJOURNAL OF BONE AND MINERAL RESEARCH, Issue 2 2002Clinton Rubin Ph.D. Abstract The skeleton's sensitivity to mechanical stimuli represents a critical determinant of bone mass and morphology. We have proposed that the extremely low level (<10 microstrain), high frequency (20-50 Hz) mechanical strains, continually present during even subtle activities such as standing are as important to defining the skeleton as the larger strains typically associated with vigorous activity (>2000 microstrain). If these low-level strains are indeed anabolic, then this sensitivity could serve as the basis for a biomechanically based intervention for osteoporosis. To evaluate this hypothesis, the hindlimbs of adult female sheep were stimulated for 20 minutes/day using a noninvasive 0.3g vertical oscillation sufficient to induce approximately 5 microstrain on the cortex of the tibia. After 1 year of stimulation, the physical properties of 10-mm cubes of trabecular bone from the distal femoral condyle of experimental animals (n = 8) were compared with controls (n = 9), as evaluated using microcomputed tomography (,CT) scanning and materials testing. Bone mineral content (BMC) was 10.6% greater (p < 0.05), and the trabecular number (Tb.N) was 8.3% higher in the experimental animals (p < 0.01), and trabecular spacing decreased by 11.3% (p < 0.01), indicating that bone quantity was increased both by the creation of new trabeculae and the thickening of existing trabeculae. The trabecular bone pattern factor (TBPf) decreased 24.2% (p < 0.03), indicating trabecular morphology adapting from rod shape to plate shape. Significant increases in stiffness and strength were observed in the longitudinal direction (12.1% and 26.7%, respectively; both, p < 0.05), indicating that the adaptation occurred primarily in the plane of weightbearing. These results show that extremely low level mechanical stimuli improve both the quantity and the quality of trabecular bone. That these deformations are several orders of magnitude below those peak strains which arise during vigorous activity indicates that this biomechanically based signal may serve as an effective intervention for osteoporosis. [source] Human Bone Cell Hyperpolarization Response to Cyclical Mechanical Strain Is Mediated by an Interleukin-1, Autocrine/Paracrine LoopJOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2000D. M. Salter Abstract Mechanical stimuli imparted by stretch, pressure, tension, fluid flow, and shear stress result in a variety of biochemical responses important in bone (re)modeling. The molecules involved in the recognition and transduction of mechanical stimuli that lead to modulation of bone cell function are not yet fully characterized. Cyclical pressure-induced strain (PIS) induces a rapid change in membrane potential of human bone cells (HBC) because of opening of membrane ion channels. This response is mediated via integrins and requires tyrosine kinase activity and an intact actin cytoskeleton. We have used this electrophysiological response to further study the signaling events occurring early after mechanical stimulation of HBC. Stimulation of HBC at 0.33Hz PIS, but not 0.104 Hz PIS, results in the production of a transferable factor that induces membrane hyperpolarization of unstimulated HBC. The production of this factor is inhibited by antibodies to ,1-integrin. Interleukin-1, (IL-1,) and prostaglandin E2 (PGE2) were identified as candidate molecules for the transferable factor as both were shown to induce HBC hyperpolarization by opening of small conductance calcium-activated potassium channels, the means by which 0.33 Hz PIS causes HBC hyperpolarization. Antibodies to IL-1,, but not other cytokines studied, inhibit the hyperpolarization response of HBC to 0.33 Hz PIS. Comparison of the signaling pathways required for 0.33 Hz PIS and IL-1,-induced membrane hyperpolarization shows that both involve the phospholipase C/inositol triphosphate pathway, protein kinase C (PKC), and prostaglandin synthesis. Unlike 0.33 Hz PIS-induced membrane hyperpolarization, IL-1,-induced hyperpolarization does not require tyrosine kinase activity or an intact actin cytoskeleton. These studies suggest that 0.33 Hz PIS of HBC induces a rapid, integrin-mediated, release of IL-1, with a subsequent autocrine/paracrine loop resulting in membrane hyperpolarization. IL-1, production in response to mechanical stimuli is potentially of importance in regulation of bone (re)modeling. [source] Mechanical loading stimulates ecto-ATPase activity in human tendon cellsJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 1 2005M. Tsuzaki Abstract Response to external stimuli such as mechanical signals is critical for normal function of cells, especially when subjected to repetitive motion. Tenocytes receive mechanical stimuli from the load-bearing matrix as tension, compression, and shear stress during tendon gliding. Overloading a tendon by high strain, shear, or repetitive motion can cause matrix damage. Injury may induce cytokine expression, matrix metalloproteinase (MMP) expression and activation resulting in loss of biomechanical properties. These changes may result in tendinosis or tendinopathy. Alternatively, an immediate effector molecule may exist that acts in a signal-dampening pathway. Adenosine 5,-triphosphate (ATP) is a candidate signal blocker of mechanical stimuli. ATP suppresses load-inducible inflammatory genes in human tendon cells in vitro. ATP and other extracellular nucleotide signaling are regulated efficiently by two distinct mechanisms: purinoceptors via specific receptor,ligand binding and ecto-nucleotidases via the hydrolysis of specific nucleotide substrates. ATP is released from tendon cells by mechanical loading or by uridine 5,-triphosphate (UTP) stimulation. We hypothesized that mechanical loading might stimulate ecto-ATPase activity. Human tendon cells of surface epitenon (TSC) and internal compartment (TIF) were cyclically stretched (1 Hz, 0.035 strain, 2 h) with or without ATP. Aliquots of the supernatant fluids were collected at various time points, and ATP concentration (ATP) was determined by a luciferin-luciferase bioluminescence assay. Total RNA was isolated from TSC and TIF (three patients) and mRNA expression for ecto-nucleotidase was analyzed by RT-PCR. Human tendon cells secreted ATP in vitro (0.5,1 nM). Exogenous ATP was hydrolyzed within minutes. Mechanical load stimulated ATPase activity. ATP was hydrolyzed in mechanically loaded cultures at a significantly greater rate compared to no load controls. Tenocytes (TSC and TIF) expressed ecto-nucleotidase mRNA (ENTPD3 and ENPP1, ENPP2). These data suggest that motion may release ATP from tendon cells in vivo, where ecto-ATPase may also be activated to hydrolyze ATP quickly. Ecto-ATPase may act as a co-modulator in ATP load-signal modulation by regulating the half-life of extracellular purine nucleotides. The extracellular ATP/ATPase system may be important for tendon homeostasis by protecting tendon cells from responding to excessive load signals and activating injurious pathways. © 2005 Wiley-Liss, Inc. [source] Annulus cells release ATP in response to vibratory loading in vitroJOURNAL OF CELLULAR BIOCHEMISTRY, Issue 4 2003Satoru Yamazaki Abstract Mechanical forces regulate the developmental path and phenotype of a variety of tissues and cultured cells. Vibratory loading as a mechanical stimulus occurs in connective tissues due to energy returned from ground reaction forces, as well as a mechanical input from use of motorized tools and vehicles. Structures in the spine may be particularly at risk when exposed to destructive vibratory stimuli. Cells from many tissues respond to mechanical stimuli, such as fluid flow, by increasing intracellular calcium concentration ([Ca2+]ic) and releasing adenosine 5,-triphosphate (ATP), extracellularly, as a mediator to activate signaling pathways. Therefore, we examined whether ATP is released from rabbit (rAN) and human (hAN) intervertebral disc annulus cells in response to vibratory loading. ATP release from annulus cells by vibratory stimulation as well as in control cells was quantitated using a firefly luciferin-luciferase assay. Cultured hAN and rAN cells had a basal level of extracellular ATP ([ATP]ec) in the range of 1,1.5 nM. Vibratory loading of hAN cells stimulated ATP release, reaching a net maximum [ATP] within 10 min of continuous vibration, and shortly thereafter, [ATP] declined and returned to below baseline level. [ATP] in the supernatant fluid of hAN cells was significantly reduced compared to the control level when the cells received vibration for longer than 15 min. In rAN cells, [ATP] was increased in response to vibratory loading, attaining a level significantly greater than that of the control after 30 min of continuous vibration. Results of the current study show that resting annulus cells secrete ATP and maintain a basal [ATP]ec. Annulus cells may use this nucleotide as a signaling messenger in an autocrine/paracrine fashion in response to vibratory loading. Rapid degradation of ATP to ADP may alternatively modulate cellular responses. It is hypothesized that exposure to repetitive, complex vibration regimens may activate signaling pathways that regulate matrix destruction in the disc. As in tendon cells, ATP may block subsequent responses to load and modulate the vibration response. Rabbit annulus cells were used as a readily obtainable source of cells in development of an animal model for testing effects of vibration on the disc. Human cells obtained from discarded surgical specimens were used to correlate responses of animal to human cells. © 2003 Wiley-Liss, Inc. [source] Influence of controlled immediate loading and implant design on peri-implant bone formationJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 2 2007Katleen Vandamme Abstract Aim: Tissue formation at the implant interface is known to be sensitive to mechanical stimuli. The aim of the study was to compare the bone formation around immediately loaded versus unloaded implants in two different implant macro-designs. Material and Methods: A repeated sampling bone chamber with a central implant was installed in the tibia of 10 rabbits. Highly controlled loading experiments were designed for a cylindrical (CL) and screw-shaped (SL) implant, while the unloaded screw-shaped (SU) implant served as a control. An F -statistic model with ,=5% determined statistical significance. Results: A significantly higher bone area fraction was observed for SL compared with SU (p<0.0001). The mineralized bone fraction was the highest for SL and significantly different from SU (p<0.0001). The chance that osteoid- and bone-to-implant contact occurred was the highest for SL and significantly different from SU (p<0.0001), but not from CL. When bone-to-implant contact was observed, a loading (SL versus SU: p=0.0049) as well as an implant geometry effect (SL versus CL: p=0.01) was found, in favour of the SL condition. Conclusions: Well-controlled immediate implant loading accelerates tissue mineralization at the interface. Adequate bone stimulation via mechanical coupling may account for the larger bone response around the screw-type implant compared with the cylindrical implant. [source] Sensory function and pain in a population of patients treated for breast cancerACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 6 2009O. J. VILHOLM Background: Chronic pain is often reported after surgery for breast cancer. This study examined pain and sensory abnormalities in women following breast cancer surgery. Methods: Sensory tests were carried out on the operated and contra-lateral side in 55 women with chronic pain after breast cancer treatment and in a reference group of 27 pain-free women, who had also undergone treatment for breast cancer. Testing included a numeric rating score of spontaneous pain, detection and pain threshold to thermal and dynamic mechanical stimuli and temporal summation to repetitive pinprick stimulation. The neuropathic pain symptom inventory was applied for participants with chronic pain. Results: The mean age was 58.6 years for the pain patients and 60.6 years for the pain-free patients. Thermal thresholds were significantly higher on the operated side than on the contra-lateral side in both groups and side difference in warmth detection threshold was significantly higher in the pain group than in the pain-free group (mean 3.8 °C vs. 1.1 °C, P=0.01). The frequency of cold allodynia was higher in participants with pain than in pain-free participants (15/53 vs. 1/25, P=0.01), and the frequency of temporal summation evoked by repetitive pinprick was higher in participants with pain than in pain-free participants (23/53 vs. 2/25, P=0.0009). The frequency of dynamic mechanical allodynia did not differ significantly between the two groups. Conclusion: These findings suggest that chronic pain after surgery for breast cancer is associated with sensory hyperexcitability and is a neuropathic pain condition. [source] Effect of dynamic loading on solute transport in soft gels implication for drug deliveryAICHE JOURNAL, Issue 3 2008F. Urciuolo Abstract Solute transport through soft gels and tissues is intimately coupled to mechanical stress and deformation of the macromolecular network. The aim of this study was to investigate the effect of periodic mechanical stimuli upon solute transport through agarose gels at different concentrations. For this purpose it was experimentally evaluated the materials parameters that govern the coupling between elasto-dynamic and solute transport: hydraulic conductivity (K), elastic modulus (HA), and macromolecular diffusivity (Dg) along with their strain dependence behavior. Mechanical activated solute transport simulation was carried out in order to elucidate the role of amplitude and frequency of soliciting mechanical stimuli on mass kinetics release. Results show that mechanical loading affects the release of macromolecules from a gel in a frequency and strain dependent manner. These findings pave the way for novel strategies for the design and engineering of smart drug delivery devices with transport mechanisms triggered by mechanical stimuli. © 2008 American Institute of Chemical Engineers AIChE J, 2008 [source] Pressure,pain threshold of oral mucosa and its region-specific modulation by pre-loadingJOURNAL OF ORAL REHABILITATION, Issue 11 2003T. Ogawa summary Once subjected to denture wearing, oral mucosa has to withstand mechanical loads of various levels and durations. However, how this load affects oral mucosal sensitivity is unknown. This study investigated the pressure,pain threshold (PPT) of oral mucosa with or without pre-loading. An electric pressure algometer was developed specifically for measuring the PPT of oral mucosa. Measurements of 10 dentulous maxillae showed that the baseline PPT (BPPT) of the palatal site was 4·9- and 3·7-fold greater than that of the labial or buccal sites, respectively. The PPT of the labial site decreased significantly compared with its BPPT after 2 s,100% BPPT and 5 s,100% BPPT pre-loading. The PPT of the palatal site increased after 5 s,50% BPPT and 5 s,80% BPPT and 0·2 s,100% BPPT and 2 s,100% BPPT pre-loading. The PPT of the buccal site did not change after all levels and durations of pre-loadings tested. These results indicated the disproportionate modulation of oral mucosal PPT following various loads, suggesting that oral mucosa possesses region-specific psychophysical tolerance to mechanical stimuli. [source] Functional integrin subunits regulating cell,matrix interactions in the intervertebral discJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2007Christopher L. Gilchrist Abstract Cellular interactions with the extracellular matrix are key factors regulating cell survival, differentiation, and response to environmental stimuli in cartilagenous tissues. Much is known about the extracellular matrix proteins in the intervertebral disc (IVD) and their variations with region, age, or degenerative state of the tissue. In contrast, little is known of the integrin cell surface receptors that directly bind to and interact with these matrix proteins in the IVD. In almost all tissues, these integrin-mediated cell,matrix interactions are important for transducing environmental cues arising from mechanical stimuli, matrix degradation fragments, and cytokines into intracellular signals. In this study, cells from the nucleus pulposus and anulus fibrosus regions of porcine IVDs were analyzed via flow cytometry to quantify integrin expression levels upon isolation and after monolayer culture. Assays of cell attachment to collagens, fibronectin, and laminin were performed after functional blocking of select integrin subunits to evaluate the role of specific integrins in cell attachment. In situ distribution and co-localization of integrins and laminin were also characterized. Results identify integrin receptors critical for IVD cell interactions with collagens (,1,1) and fibronectin (,5,1). Additionally, dramatic differences in cell,laminin interactions were observed between cells of the nucleus and anulus regions, including differences in ,6 integrin expression, cell adhesion to laminin, and in situ pericellular environments. These findings suggest laminin,cell interactions may be important and unique to the nucleus pulposus region of the IVD. The results of this study provide new information on functional cell,matrix interactions in tissues of the IVD. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25: 829,840, 2007 [source] Microenvironment regulation of PRG4 phenotype of chondrocytesJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 5 2007Megan E. Blewis Abstract Articular cartilage is a heterogeneous tissue with superficial (S), middle (M), and deep (D) zones. Chondrocytes in the S zone secrete the lubricating PRG4 protein, while chondrocytes from the M and D zones are more specialized in producing large amounts of the glycosaminoglycan (GAG) component of the extracellular matrix. Soluble and insoluble chemicals and mechanical stimuli regulate cartilage development, growth, and homeostasis; however, the mechanisms of regulation responsible for the distinct PRG4-positive and negative phenotypes of chondrocytes are unknown. The objective of this study was to determine if interaction between S and M chondrocytes regulates chondrocyte phenotype, as determined by coculture in monolayer at different ratios of S:M (100:0, 75:25, 50:50, 25:75, 0:100) and at different densities (240,000, 120,000, 60,000, and 30,000 cells/cm2), and by measurement of PRG4 secretion and expression, and GAG accumulation. Coculture of S and M cells resulted in significant up-regulation in PRG4 secretion and the percentage of cells expressing PRG4, with simultaneous down-regulation of GAG accumulation. Tracking M cells with PKH67 dye in coculture revealed that they maintained a PRG4-negative phenotype, and proliferated less than S cells. Taken together, these results indicate that the up-regulated PRG4 expression in coculture is a result of preferential proliferation of PRG4-expressing S cells. This finding may have practical implications for generating a large number of phenotypically normal S cells, which can be limited in source, for tissue engineering applications. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:685,695, 2007 [source] Differential effects of static and dynamic compression on meniscal cell gene expressionJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 6 2003Maureen L. Upton Abstract Cells of the meniscus are exposed to a wide range of time-varying mechanical stimuli that may regulate their metabolic activity in vivo. In this study, the biological response of the meniscus to compressive stimuli was evaluated in vitro, using a well-controlled explant culture system. Gene expression for relevant extracellular matrix proteins was quantified using real-time RT-PCR following a 24 h period of applied static (0.1 MPa compressive stress) or dynamic compression (0.08,0.16 MPa). Static and dynamic compression were found to differentially regulate mRNA levels for specific proteins of the extracellular matrix. Decreased mRNA levels were observed for decorin (,2.1 fold-difference) and type II collagen (,4.0 fold-difference) following 24 h of dynamic compression. Decorin mRNA levels also decreased following static compression (,4.5 fold-difference), as did mRNA levels for both types I (,3.3 fold-difference) and II collagen (,4.0 fold-difference). Following either static or dynamic compression, mRNA levels for aggrecan, biglycan and cytoskeletal proteins were unchanged. It is noteworthy that static compression was associated with a 2.6 fold-increase in mRNA levels for collagenase, or MMP-1, suggesting that the homeostatic balance between collagen biosynthesis and catabolism was altered by the mechanical stimuli. These findings demonstrate that the biosynthetic response of the meniscus to compression is regulated, in part, at the transcriptional level and that transcription of types I and II collagen as well as decorin may be regulated by common mechanical stimuli. © 2003 Orthopaedic Research Society. Published by Elsevier Science Ltd. All rights reserved. [source] Compressive compared with tensile loading of medial collateral ligament scar in vitro uniquely influences mRNA levels for aggrecan, collagen type II, and collagenaseJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 4 2000Tokifumi Majima To test the hypothesis that loading conditions can be used to engineer early ligament scar behaviors, we used an in vitro system to examine the effect that cyclic hydrostatic compression and cyclic tension applied to 6-week rabbit medial collateral ligament scars had on mRNA levels for matrix molecules, collagenase, and the proto-oncogenes c-fos and c-jun. Our specific hypothesis was that tensile stress would promote more normal mRNA expression in ligament whereas compression would lead to higher levels of mRNA for cartilage-like molecules. Femur (injured medial collateral ligament)-tibia complexes were subjected to a hydrostatic pressure of 1 MPa or a tensile stress of 1 MPa of 0.5 Hz for 1 minute followed by 14 minutes of rest. On the basis of a preliminary optimization experiment, this 15-minute testing cycle was repeated for 4 hours. Semiquantitative reverse transcription-polymerase chain reaction analysis was performed for mechanically treated medial collateral ligament scars with use of rabbit specific primer sets for types I, II, and III collagen, decorin, biglycan, fibromodulin, versican, aggrecan, collagenase, c-fos, c-jun, and a housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. Cyclic hydrostatic compression resulted in a statistically significant increase in mRNA levels of type-II collagen (171% of nonloaded values) and aggrecan (313% of nonloaded values) but statistically significant decreases in collagenase mRNA levels (35% of nonloaded values). Cyclic tension also resulted in a statistically significant decrease in collagenase mRNA levels (66% of nonloaded values) and an increase in aggrecan mRNA levels (458% of nonloaded values) but no significant change in the mRNA levels for the other molecules. The results show that it is possible to alter mRNA levels for a subset of genes in scar tissue by supplying unique mechanical stimuli in vitro and thus that further investigation of scar engineering for potential reimplantation appears feasible. [source] The structure and function of auditory chordotonal organs in insectsMICROSCOPY RESEARCH AND TECHNIQUE, Issue 6 2004Jayne E. Yack Abstract Insects are capable of detecting a broad range of acoustic signals transmitted through air, water, or solids. Auditory sensory organs are morphologically diverse with respect to their body location, accessory structures, and number of sensilla, but remarkably uniform in that most are innervated by chordotonal organs. Chordotonal organs are structurally complex Type I mechanoreceptors that are distributed throughout the insect body and function to detect a wide range of mechanical stimuli, from gross motor movements to air-borne sounds. At present, little is known about how chordotonal organs in general function to convert mechanical stimuli to nerve impulses, and our limited understanding of this process represents one of the major challenges to the study of insect auditory systems today. This report reviews the literature on chordotonal organs innervating insect ears, with the broad intention of uncovering some common structural specializations of peripheral auditory systems, and identifying new avenues for research. A general overview of chordotonal organ ultrastructure is presented, followed by a summary of the current theories on mechanical coupling and transduction in monodynal, mononematic, Type 1 scolopidia, which characteristically innervate insect ears. Auditory organs of different insect taxa are reviewed, focusing primarily on tympanal organs, and with some consideration to Johnston's and subgenual organs. It is widely accepted that insect hearing organs evolved from pre-existing proprioceptive chordotonal organs. In addition to certain non-neural adaptations for hearing, such as tracheal expansion and cuticular thinning, the chordotonal organs themselves may have intrinsic specializations for sound reception and transduction, and these are discussed. In the future, an integrated approach, using traditional anatomical and physiological techniques in combination with new methodologies in immunohistochemistry, genetics, and biophysics, will assist in refining hypotheses on how chordotonal organs function, and, ultimately, lead to new insights into the peripheral mechanisms underlying hearing in insects. Microsc. Res. Tech. 63:315,337, 2004. © 2004 Wiley-Liss, Inc. [source] Signaling satellite-cell activation in skeletal muscle: Markers, models, stretch, and potential alternate pathwaysMUSCLE AND NERVE, Issue 3 2005Ashley C. Wozniak BSc Abstract Activation of skeletal muscle satellite cells, defined as entry to the cell cycle from a quiescent state, is essential for normal growth and for regeneration of tissue damaged by injury or disease. This review focuses on early events of activation by signaling through nitric oxide and hepatocyte growth factor, and by mechanical stimuli. The impact of various model systems used to study activation and the regulation of satellite-cell quiescence are placed in the context of activation events in other tissues, concluding with a speculative model of alternate pathways signaling satellite-cell activation. Muscle Nerve, 2005 [source] Activation of splanchnic and pelvic colonic afferents by bradykinin in miceNEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2005S. M. Brierley Abstract, Background:, Lumbar splanchnic (LSN) and sacral pelvic (PN) nerves convey different mechanosensory information from the colon to the spinal cord. Here, we determined whether these pathways differ also in their chemosensitivity to bradykinin. Methods:, Using a novel in vitro mouse colon preparation, serosal afferents were recorded from the LSN and PN and distinguished based on their mechanosensitivity to von Frey filaments (70,4000 mg) and insensitivity to colonic stretch (1,5 g) or fine mucosal stroking (10 mg). Bradykinin was applied into a ring around mechanoreceptive fields. Results:, The LSN and PN afferents had different dynamic responses to mechanical stimuli: PN afferents required lower intensity stimuli, evoked larger responses, and displayed more maintained responses than LSN afferents. Bradykinin (1 ,mol L,1) excited 66% (27 of 41) of LSN afferents. Responses to probing were potentiated after bradykinin. The concentration-dependent (EC50: 0.16 ,mol L,1) response was reversed by the B2 -receptor antagonist HOE-140 (10 nmol L,1). Twelve bradykinin responsive afferents were mechanically insensitive. More LSN serosal afferents responded to bradykinin than PN afferents (11%, P < 0.001) , with larger responses (P < 0.05). No mechanically insensitive PN afferents were recruited by bradykinin. Conclusions:, Bradykinin potently stimulates most splanchnic serosal afferents via B2 -receptors, but few pelvic afferents. Mechanically insensitive afferents recruited by bradykinin are exclusive to the LSN. [source] Design and assessment of a tissue-engineered model of human phalanges and a small jointORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 4 2005WJ Landis Structured Abstract Authors ,, Landis WJ, Jacquet R, Hillyer J, Lowder E, Yanke A, Siperko L, Asamura S, Kusuhara H, Enjo M, Chubinskaya S, Potter K, Isogai N. Objectives ,, To develop models of human phalanges and small joints by suturing different cell-polymer constructs that are then implanted in athymic (nude) mice. Design ,, Models consisted of bovine periosteum, cartilage, and/or tendon cells seeded onto biodegradable polymer scaffolds of either polyglycolic acid (PGA) or copolymers of PGA and poly-L-lactic acid (PLLA) or poly- , -caprolactone (PCL) and PLLA. Constructs were fabricated to produce a distal phalanx, middle phalanx, or distal interphalangeal joint. Setting and Sample Population ,, Studies of more than 250 harvested implants were conducted at the Northeastern Ohio Universities College of Medicine. Experimental Variable ,, Polymer scaffold, cell type, and implantation time were examined. Outcome Measure ,, Tissue-engineered specimens were characterized by histology, transmission electron microscopy, in situ hybridization, laser capture microdissection and qualitative and quantitative polymerase chain reaction analysis, magnetic resonance microscopy, and X-ray microtomography. Results ,, Over periods to 60 weeks of implantation, constructs developed through vascularity from host mice; formed new cartilage, bone, and/or tendon; expressed characteristic genes of bovine origin, including type I, II and X collagen, osteopontin, aggrecan, biglycan, and bone sialoprotein; secreted corresponding proteins; responded to applied mechanical stimuli; and maintained shapes of human phalanges with small joints. Conclusion ,, Results give insight into construct processes of tissue regeneration and development and suggest more complete tissue-engineered cartilage, bone, and tendon models. These should have significant future scientific and clinical applications in medicine, including their use in plastic surgery, orthopaedics, craniofacial reconstruction, and teratology. [source] Pressure simulation of orthodontic force in osteoblasts: a pilot studyORTHODONTICS & CRANIOFACIAL RESEARCH, Issue 1 2004U. Baumert Structured Abstract Authors , Baumert U, Golan I, Becker B, Hrala BP, Redlich M, Roos HA, Reichenberg E, Palmon A, Müßig D Objectives , To elucidate the RUNX2 gene expression induction in human osteoblasts after mechanical loading. Design , Using a stringent pulse-chase protocol human osteoblasts were exposed to centrifugal pressure force for 30 and 90 min. Untreated control cells were processed in parallel. Before, and at defined times after centrifugation, total RNA was isolated. RUNX2 gene expression was measured using real-time quantitative reverse transcriptase polymerase chain reaction. The stress/control ratio was used to illustrate possible stimulatory or diminishing effects of force application. Results , Immediately after 30 min of force application the RUNX2 gene expression was induced by a factor of 1.7 ± 0.14 as compared with the negative control. This induction decreased rapidly and reached its pre-load levels within 30 min. Longer force applications (up to 90 min) did not change the RUNX2 gene expression. Conclusion , In mature osteoblasts centrifugal pressure force stimulates RUNX2 gene expression within a narrow time frame: loading of mature cells results in a temporary increase of RUNX2 expression and a fast downregulation back to its pre-load expression level. With this pilot study the gene expression behavior after mechanical stimuli could be determined with a simple laboratory setup. [source] Photoplastic effects in chalcogenide glasses: A reviewPHYSICA STATUS SOLIDI (B) BASIC SOLID STATE PHYSICS, Issue 8 2009S. N. Yannopoulos Abstract A synopsis of various photoinduced changes of rheological, mechanical and elastic properties is presented in the first part of the article. After a critical appraisal of a large body of experimental data, it is suggested that the photoviscous effect, that is, the athermal decrease of viscosity of a non-crystalline chalcogenide upon illumination, is the key for a plethora of photoinduced effects reported so far in the literature under different names. Morphic effects (shape or surface morphology) may appear either in the presence or absence of external mechanical stimuli leading to the fabrication of a variety of technologically important photoprocessed structures. A few representative examples of photoplastic effects are described in some detail in the second part of the paper, based on information provided by in situ Raman scattering and nanoindentation experiments. [source] Pheromones in relation to aggregation and reproduction in desert locustsPHYSIOLOGICAL ENTOMOLOGY, Issue 1 2003Hans-Jörg Ferenz Abstract. Desert locusts, Schistocerca gregaria (Forskål) (Orthoptera: Acrididae), exhibit a population density-dependent phase polymorphism which includes the gradual change of many morphological, physiological and behavioural characteristics. Many volatiles associated with desert locusts have been identified recently and it is assumed that they are involved in pheromonal control of behaviour and development of locusts. Ovipositing females deposit with their egg pods several volatiles that appear to be attractive to other females resulting , possibly in combination with environmental factors , in an aggregated oviposition. Mature males release several volatiles, among them phenylacetonitrile, which are reported to accelerate sexual maturation in young males. Also, aggregation pheromone systems for hoppers and adults have been described. However, recent studies and publications shed a new light on the postulated effects of some of these volatiles. Gregarious behaviour can undoubtedly be induced by mechanical stimuli. Furthermore, the main component of the adult aggregation pheromone system, phenylacetonitrile, is found to be a repellent obviously not involved in aggregation. Comprehensive studies have demonstrated that phenylacetonitrile is used by mature gregarious males as a courtship inhibition pheromone to enhance mate guarding. Recent progress, contradictory results and perspectives in desert locust pheromone research related to reproduction are summarized and discussed in this paper. [source] Functional significance of genetic variation underlying limb bone diaphyseal structureAMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY, Issue 1 2010Ian J. Wallace Abstract Limb bone diaphyseal structure is frequently used to infer hominin activity levels from skeletal remains, an approach based on the well-documented ability of bone to adjust to its loading environment during life. However, diaphyseal structure is also determined in part by genetic factors. This study investigates the possibility that genetic variation underlying diaphyseal structure is influenced by the activity levels of ancestral populations and might also have functional significance in an evolutionary context. We adopted an experimental evolution approach and tested for differences in femoral diaphyseal structure in 1-week-old mice from a line that had been artificially selected (45 generations) for high voluntary wheel running and non-selected controls. As adults, selected mice are significantly more active on wheels and in home cages, and have thicker diaphyses. Structural differences at 1 week can be assumed to primarily reflect the effects of selective breeding rather than direct mechanical stimuli, given that the onset of locomotion in mice is shortly after Day 7. We hypothesized that if genetically determined diaphyseal structure reflects the activity patterns of members of a lineage, then selected animals will have relatively larger diaphyseal dimensions at 1 week compared to controls. The results provide strong support for this hypothesis and suggest that limb bone cross sections may not always only reflect the activity levels of particular fossil individuals, but also convey an evolutionary signal providing information about hominin activity in the past. Am J Phys Anthropol 143:21,30, 2010. © 2010 Wiley-Liss, Inc. [source] | ||||||||||||||||||||||||||||||||||