Microgravity Science and Technology

, Volume 30, Issue 4, pp 469–481 | Cite as

Finite Element Analysis of Osteocytes Mechanosensitivity Under Simulated Microgravity

  • Xiao Yang
  • Lian-Wen SunEmail author
  • Cheng-Fei Du
  • Xin-Tong Wu
  • Yu-Bo FanEmail author
Original Article


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.


Finite element Osteocytes Mechanical deformation Simulated microgravity 



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.


  1. 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)CrossRefGoogle Scholar
  2. 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)CrossRefGoogle Scholar
  3. 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)CrossRefGoogle Scholar
  4. 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)CrossRefGoogle Scholar
  5. 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)CrossRefGoogle Scholar
  6. 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)CrossRefGoogle Scholar
  7. Bonewald, L.F.: The amazing osteocyte. J. Bone Miner. Res. 26(2), 229–38 (2011)CrossRefGoogle Scholar
  8. 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)CrossRefGoogle Scholar
  9. Dahl, K.N., Kalinowski, A., Pekkan, K.: Mechanobiology and the microcirculation: cellular, nuclear and fluid mechanics. Microcirculation 17(3), 179–91 (2010)CrossRefGoogle Scholar
  10. 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)CrossRefGoogle Scholar
  11. 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)CrossRefGoogle Scholar
  12. Fletcher, D.A., Mullins, R.D.: Cell mechanics and the cytoskeleton. Nature 463(7280), 485–92 (2010)CrossRefGoogle Scholar
  13. Galli, C., Passeri, G., Macaluso, G.M.: Osteocytes and WNT: the mechanical control of bone formation. J. Dent. Res. 89(4), 331–43 (2010)CrossRefGoogle Scholar
  14. Haase, K., Pelling, A.E.: The role of the actin cortex in maintaining cell shape. Commun. Integr. Biol. 6 (6), e26714 (2013)CrossRefGoogle Scholar
  15. 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)CrossRefGoogle Scholar
  16. Ingber, D.E., Tensegrity, I.: Cell structure and hierarchical systems biology. J. Cell Sci. 116(Pt 7), 1157–73 (2003)CrossRefGoogle Scholar
  17. Ingber, D.E., Wang, N., Stamenovic, D.: Tensegrity, cellular biophysics, and the mechanics of living systems. Rep. Prog. Phys. 77(4), 046603 (2014)MathSciNetCrossRefGoogle Scholar
  18. 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)CrossRefGoogle Scholar
  19. Jacobs, C.R., Temiyasathit, S., Castillo, A.B.: Osteocyte mechanobiology and pericellular mechanics. Annu. Rev. Biomed. Eng. 12, 369–400 (2010)CrossRefGoogle Scholar
  20. 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)CrossRefGoogle Scholar
  21. 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)CrossRefGoogle Scholar
  22. Khayyeri, H., Barreto, S., Lacroix D.: Primary cilia mechanics affects cell mechanosensation: a computational study. J. Theor. Biol. 379, 38–46 (2015)CrossRefGoogle Scholar
  23. 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)CrossRefGoogle Scholar
  24. 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)CrossRefGoogle Scholar
  25. 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)CrossRefGoogle Scholar
  26. Lirani-Galvao, A.P., Lazaretti-Castro, M.: Physical approach for prevention and treatment of osteoporosis. Arq. Bras. Endocrinol. Metabol. 54(2), 171–8 (2010)CrossRefGoogle Scholar
  27. 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)CrossRefGoogle Scholar
  28. 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 33-4CrossRefGoogle Scholar
  29. 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)CrossRefGoogle Scholar
  30. 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
  31. 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)CrossRefGoogle Scholar
  32. 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
  33. 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)CrossRefGoogle Scholar
  34. 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
  35. Robling, A.G., Castillo, A.B., Turner, C.H.: Biomechanical and molecular regulation of bone remodeling. Annu. Rev. Biomed. Eng. 8, 455–498 (2006)CrossRefGoogle Scholar
  36. Stricker, J., Falzone, T., Gardel, M.L.: Mechanics of the F-actin cytoskeleton. J. Biomech. 43(1), 9–14 (2010)CrossRefGoogle Scholar
  37. Tatsumi, S., Ishii, K., Amizuka, N., et al.: Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab. 5(6), 464–75 (2007)CrossRefGoogle Scholar
  38. 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)CrossRefGoogle Scholar
  39. 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)CrossRefGoogle Scholar
  40. 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
  41. Watanabe, K., Ikeda, K.: Osteocytes in Normal Physiology and Osteoporosis. Crit. Rev. Bone Miner. Metab. 8(4), 224–32 (2010)CrossRefGoogle Scholar
  42. 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)CrossRefGoogle Scholar
  43. 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)CrossRefGoogle Scholar
  44. 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)CrossRefGoogle Scholar
  45. Young, Y.N., Downs, M., Jacobs, C.R.: Dynamics of the primary cilium in shear flow. Biophys. J 103 (4), 629–39 (2012)CrossRefGoogle Scholar
  46. 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)CrossRefGoogle Scholar
  47. 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)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina
  2. 2.Key Laboratory for Biomechanics and Mechanobiology of Ministry of EducationBeihang UniversityBeijingChina
  3. 3.Beijing Advanced Innovation Center for Biomedical EngineeringBeihang UniversityBeijingChina
  4. 4.Tianjin Key Laboratory for Advanced Mechatronic System Design and Intelligent ControlTianjin University of TechnologyTianjinChina
  5. 5.Beijing Key Laboratory of Rehabilitation Technical Aids for Old-Age DisabilityNational Research Center for Rehabilitation Technical AidsBeijingChina

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