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Finite Element Analysis of Osteocytes Mechanosensitivity Under Simulated Microgravity

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Abstract

It was found that the mechanosensitivity of osteocytes could be altered under simulated microgravity. However, how the mechanical stimuli as the biomechanical origins cause the bioresponse in osteocytes under microgravity is unclear yet. Computational studies may help us to explore the mechanical deformation changes of osteocytes under microgravity. Here in this paper, we intend to use the computational simulation to investigate the mechanical behavior of osteocytes under simulated microgravity. In order to obtain the shape information of osteocytes, the biological experiment was conducted under simulated microgravity prior to the numerical simulation The cells were rotated by a clinostat for 6 hours or 5 days and fixed, the cytoskeleton and the nucleus were immunofluorescence stained and scanned, and the cell shape and the fluorescent intensity were measured from fluorescent images to get the dimension information of osteocytes The 3D finite element (FE) cell models were then established based on the scanned image stacks. Several components such as the actin cortex, the cytoplasm, the nucleus, the cytoskeleton of F-actin and microtubules were considered in the model. The cell models in both 6 hours and 5 days groups were then imposed by three magnitudes (0.5, 10 and 15 Pa) of simulating fluid shear stress, with cell total displacement and the internal discrete components deformation calculated. The results showed that under the simulated microgravity: (1) the nuclear area and height statistically significantly increased, which made the ratio of membrane-cortex height to nucleus height statistically significantly decreased; (2) the fluid shear stress-induced maximum displacements and average displacements in the whole cell decreased, with the deformation decreasing amplitude was largest when exposed to 1.5Pa of fluid shear stress; (3) the fluid shear stress-induced deformation of cell membrane-cortex and cytoskeleton decreased, while the fluid shear stress-induced deformation of nucleus increased. The results suggested the mechanical behavior of whole osteocyte cell body was suppressed by simulated microgravity, and this decrement was enlarged with either the increasing amplitude of fluid shear stress or the duration of simulated microgravity. What’s more, the mechanical behavior of membrane-cortex and cytoskeleton was suppressed by the simulated microgravity, which indicated the mechanotransduction process in the cell body may be further inhibited. On the contrary, the cell nucleus deformation increased under simulated microgravity, which may be related to either the decreased amount of cytoskeleton or the increased volume occupied proportion of nucleus in whole cell under the simulated microgravity. The numerical results supported our previous biological experiments, and showed particularly affected cellular components under the simulated microgravity. The computational study here may help us to better understand the mechanism of mechanosensitivity changes in osteocytes under simulated microgravity, and further to explore the mechanism of the bone loss in space flight.

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References

  • Aguirre, J.I., Plotkin, L., Stewart, S.A., et al.: Osteocyte apoptosis is induced by weightlessness in mice and precedes osteoclast recruitment and bone loss. J. Bone Miner. Res. 21(4), 605–15 (2006)

    Article  Google Scholar 

  • Bacabac, R.G., Smit, T.H., Mullender, M.G., et al.: Nitric oxide production by bone cells is fluid shear stress rate dependent. Biochem. Biophys. Res. Commun. 315(4), 823–829 (2004)

    Article  Google Scholar 

  • Bacabac, R.G., Loon, J.J.W.A.V., Blieck-Hogervorst, J.M.A.d., et al.: Microgravity and Bone Cell Mechanosensitivity: FLOW experiment during the DELTA mission. Microgravity Sci. Technol. 19(5/6), 133–37 (2007)

    Article  Google Scholar 

  • Baik, A.D., Lu, X.L., Qiu, J., et al.: Quasi-3d cytoskeletal dynamics of osteocytes under fluid flow. Biophys. J 99(9), 2812–20 (2010)

    Article  Google Scholar 

  • Baik, A.D., Qiu, J., Hillman, E.M., et al.: Simultaneous tracking of 3D actin and microtubule strains in individual MLO-y4 osteocytes under oscillatory flow. Biochem. Biophys. Res. Commun. 431(4), 718–23 (2013)

    Article  Google Scholar 

  • Barreto, S., Clausen, C.H., Perrault, C.M., et al.: A multi-structural single cell model of force-induced interactions of cytoskeletal components. Biomaterials 34(26), 6119–6126 (2013)

    Article  Google Scholar 

  • Bonewald, L.F.: The amazing osteocyte. J. Bone Miner. Res. 26(2), 229–38 (2011)

    Article  Google Scholar 

  • Canciani, B., Ruggiu, A., Giuliani, A., et al.: Effects of long time exposure to simulated micro- and hypergravity on skeletal architecture. J. Mech. Behav. Biomed. Mater. 51, 1–12 (2015)

    Article  Google Scholar 

  • Dahl, K.N., Kalinowski, A., Pekkan, K.: Mechanobiology and the microcirculation: cellular, nuclear and fluid mechanics. Microcirculation 17(3), 179–91 (2010)

    Article  Google Scholar 

  • Dai, Z.Q., Li, Y., Ding, B., et al.: Actin microfilaments participate in the regulation of the COL1a1 promoter activity in ROS17/2.8 cells under simulated microgravity. Adv. Space Res. 38, 1159–1167 (2006)

    Article  Google Scholar 

  • Dowling, E.P., Ronan, W., McGarry, J.P.: Computational investigation of in situ chondrocyte deformation and actin cytoskeleton remodelling under physiological loading. Acta. Biomater 9(4), 5943–55 (2013)

    Article  Google Scholar 

  • Fletcher, D.A., Mullins, R.D.: Cell mechanics and the cytoskeleton. Nature 463(7280), 485–92 (2010)

    Article  Google Scholar 

  • Galli, C., Passeri, G., Macaluso, G.M.: Osteocytes and WNT: the mechanical control of bone formation. J. Dent. Res. 89(4), 331–43 (2010)

    Article  Google Scholar 

  • Haase, K., Pelling, A.E.: The role of the actin cortex in maintaining cell shape. Commun. Integr. Biol. 6 (6), e26714 (2013)

    Article  Google Scholar 

  • Herranz, R., Anken, R., Boonstra, J., et al.: Ground-based facilities for simulation of microgravity: organism-specific recommendations for their use, and recommended terminology. Astrobiology 13(1), 1–17 (2013)

    Article  Google Scholar 

  • Ingber, D.E., Tensegrity, I.: Cell structure and hierarchical systems biology. J. Cell Sci. 116(Pt 7), 1157–73 (2003)

    Article  Google Scholar 

  • Ingber, D.E., Wang, N., Stamenovic, D.: Tensegrity, cellular biophysics, and the mechanics of living systems. Rep. Prog. Phys. 77(4), 046603 (2014)

    Article  MathSciNet  Google Scholar 

  • Jaasma, M.J., Jackson, W.M., Keaveny, T.M.: The effects of morphology, confluency, and phenotype on whole-cell mechanical behavior. Ann. Biomed. Eng. 34(5), 759–68 (2006)

    Article  Google Scholar 

  • Jacobs, C.R., Temiyasathit, S., Castillo, A.B.: Osteocyte mechanobiology and pericellular mechanics. Annu. Rev. Biomed. Eng. 12, 369–400 (2010)

    Article  Google Scholar 

  • Jean, R.P., Chen, C.S., Spector, A.A.: Finite-Element analysis of the Adhesion-Cytoskeleton-Nucleus mechanotransduction pathway during endothelial cell rounding axisymmetric model. J. Biomech. Eng. 127(4), 594–600 (2005)

    Article  Google Scholar 

  • Kardas, D., Nackenhorst, U., Balzani, D.: Computational model for the cell-mechanical response of the osteocyte cytoskeleton based on self-stabilizing tensegrity structures. Biomech. Model. Mechanobiol. 12(1), 167–183 (2013)

    Article  Google Scholar 

  • Khayyeri, H., Barreto, S., Lacroix D.: Primary cilia mechanics affects cell mechanosensation: a computational study. J. Theor. Biol. 379, 38–46 (2015)

    Article  Google Scholar 

  • Lang, T.F., Leblanc, A.D., Evans, H.J., et al.: Adaptation of the proximal femur to skeletal reloading after long-duration space flight. J. Bone Miner. Res. 21(8), 1224–1230 (2006)

    Article  Google Scholar 

  • Lau, E., Al-Dujaili, S., Guenther, A., et al.: Effect of low-magnitude, high-frequency vibration on osteocytes in the regulation of osteoclasts. Bone 46(6), 1508–1515 (2010)

    Article  Google Scholar 

  • Li, W.T., Huang, Y.F., Sun, L.W., et al.: Would interstitial fluid flow be responsible for skeletal maintenance in tail-suspended rats? Microgravity Sci. Technol. 29(1-2), 107–114 (2017)

    Article  Google Scholar 

  • Lirani-Galvao, A.P., Lazaretti-Castro, M.: Physical approach for prevention and treatment of osteoporosis. Arq. Bras. Endocrinol. Metabol. 54(2), 171–8 (2010)

    Article  Google Scholar 

  • Lombardi, M.L., Jaalouk, D.E., Shanahan, C.M., et al.: The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton. J. Biol. Chem. 286 (30), 26743–53 (2011)

    Article  Google Scholar 

  • McGarry, J.G., Prendergast, P.J.: A three-dimensional finite element model of an adherent eukaryotic cell. Eur. Cell. Mater. 7, 27–33 (2004). discussion 33-4

    Article  Google Scholar 

  • McGarry, J.G., Klein-Nulend, J., Mullender, M.G., et al.: A comparison of strain and fluid shear stress in stimulating bone cell responses–a computational and experimental study. FASEB J 19(3), 482–4 (2005)

    Article  Google Scholar 

  • Nagaraja, M.P., Jo, H.: The role of mechanical stimulation in recovery of bone Loss-High versus low magnitude and frequency of force. Life (Basel) 4(2), 117–30 (2014)

    Google Scholar 

  • Nickerson, C.A., Ott, C.M., Mister, S.J., et al.: Microgravity as a novel environmental signal affecting Salmonella enterica serovar Typhimurium virulence. Infect. Immun. 68(6), 3147–52 (2000)

    Article  Google Scholar 

  • Ohshima, H., Matsumoto, T.: [Space flight/bedrest immobilization and bone. Bone metabolism in space flight and long-duration bed rest]. Clin. Calcium 22(12), 1803–12 (2012)

    Google Scholar 

  • Ren, L., Yang, P., Wang, Z., et al.: Biomechanical and biophysical environment of bone from the macroscopic to the pericellular and molecular level. J. Mech. Behav. Biomed. Mater. 50, 104–22 (2015)

    Article  Google Scholar 

  • Ribeiro, A.S., Dahl, K.N.: The nucleus as a central structure in defining the mechanical properties of stem cells. Conf. Proc. IEEE Eng. Med. Biol. Soc. 2010, 831–4 (2010)

    Google Scholar 

  • Robling, A.G., Castillo, A.B., Turner, C.H.: Biomechanical and molecular regulation of bone remodeling. Annu. Rev. Biomed. Eng. 8, 455–498 (2006)

    Article  Google Scholar 

  • Stricker, J., Falzone, T., Gardel, M.L.: Mechanics of the F-actin cytoskeleton. J. Biomech. 43(1), 9–14 (2010)

    Article  Google Scholar 

  • Tatsumi, S., Ishii, K., Amizuka, N., et al.: Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 5(6), 464–75 (2007)

    Article  Google Scholar 

  • Vorselen, D., Roos, W.H., Mackintosh, F.C., et al.: The role of the cytoskeleton in sensing changes in gravity by nonspecialized cells. FASEB J 28(2), 536–47 (2014)

    Article  Google Scholar 

  • Wang, H., Ji, B., Liu, X.S., et al.: Osteocyte-viability-based simulations of trabecular bone loss and recovery in disuse and reloading. Biomech. Model. Mechanobiol. 13(1), 153–66 (2014)

    Article  Google Scholar 

  • Wang, L., Dong, J., Xian, C.J.: Strain amplification analysis of an osteocyte under static and cyclic loading: a finite element study. Biomed. Res. Int. 2015, 376474 (2015)

    Google Scholar 

  • Watanabe, K., Ikeda, K.: Osteocytes in Normal Physiology and Osteoporosis. Crit. Rev. Bone Miner. Metab. 8(4), 224–32 (2010)

    Article  Google Scholar 

  • Xue, F., Lennon, A.B., McKayed, K.K., et al.: Effect of membrane stiffness and cytoskeletal element density on mechanical stimuli within cells: an analysis of the consequences of ageing in cells. Comput. Methods Biomech. Biomed. Engin. 18(5), 468–76 (2015)

    Article  Google Scholar 

  • Yang, X., Sun, L. -W., Wu, X. -T., et al.: Impact of shear stress and simulated microgravity on osteocytes using a new rotation cell culture device. Acta Astronaut. 116, 286–298 (2015)

    Article  Google Scholar 

  • Yang, X., Sun, L.-w., Wu, X.-t., et al.: Effect of simulated microgravity on osteocytes responding to fluid shear stress. Acta Astronaut. 2013(84), 237–243 (2013)

    Article  Google Scholar 

  • Young, Y.N., Downs, M., Jacobs, C.R.: Dynamics of the primary cilium in shear flow. Biophys. J 103 (4), 629–39 (2012)

    Article  Google Scholar 

  • Zeng, Y., Yip, A.K., Teo, S.K., et al.: A three-dimensional random network model of the cytoskeleton and its role in mechanotransduction and nucleus deformation. Biomech. Model. Mechanobiol. 11(1-2), 49–59 (2012)

    Article  Google Scholar 

  • Zhang, J., Li, J.B., Xu, H.Y., et al.: Responds of bone cells to microgravity: Ground-based research. Microgravity Sci. Technol. 27(6), 455–464 (2015)

    Article  Google Scholar 

Download references

Acknowledgements

This work was funded by grants from the National Natural Science Foundation of China (No. 11472033 and No.11421202), the 111 Project (No. B13003), the National Key Research and Development Plan (2016YFC1101101), and the Third Young Elite Scientist Sponsorship Program by China Association for Science and Technology.

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Authors and Affiliations

  1. School of Biological Science and Medical Engineering, Beihang University, Beijing, 100083, China

    Xiao Yang, Lian-Wen Sun, Cheng-Fei Du, Xin-Tong Wu & Yu-Bo Fan

  2. Key Laboratory for Biomechanics and Mechanobiology of Ministry of Education, Beihang University, Beijing, 100083, China

    Xiao Yang, Lian-Wen Sun, Cheng-Fei Du, Xin-Tong Wu & Yu-Bo Fan

  3. Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, Beijing, 100191, China

    Xiao Yang, Lian-Wen Sun & Yu-Bo Fan

  4. Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent Control, Tianjin University of Technology, 300384, Tianjin, China

    Cheng-Fei Du

  5. Beijing Key Laboratory of Rehabilitation Technical Aids for Old-Age Disability, National Research Center for Rehabilitation Technical Aids, Beijing, 100176, China

    Yu-Bo Fan

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  1. Xiao Yang
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Correspondence to Lian-Wen Sun or Yu-Bo Fan.

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Yang, X., Sun, LW., Du, CF. et al. Finite Element Analysis of Osteocytes Mechanosensitivity Under Simulated Microgravity. Microgravity Sci. Technol. 30, 469–481 (2018). https://doi.org/10.1007/s12217-018-9613-x

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