Biomechanics and Modeling in Mechanobiology

, Volume 13, Issue 4, pp 851–860 | Cite as

Interstitial fluid flow in canaliculi as a mechanical stimulus for cancellous bone remodeling: in silico validation

Original Paper

Abstract

Cancellous bone has a dynamic 3-dimensional architecture of trabeculae, the arrangement of which is continually reorganized via bone remodeling to adapt to the mechanical environment. Osteocytes are currently believed to be the major mechanosensory cells and to regulate osteoclastic bone resorption and osteoblastic bone formation in response to mechanical stimuli. We previously developed a mathematical model of trabecular bone remodeling incorporating the possible mechanisms of cellular mechanosensing and intercellular communication in which we assumed that interstitial fluid flow activates the osteocytes to regulate bone remodeling. While the proposed model has been validated by the simulation of remodeling of a single trabecula, it remains unclear whether it can successfully represent in silico the functional adaptation of cancellous bone with its multiple trabeculae. In the present study, we demonstrated the response of cancellous bone morphology to uniaxial or bending loads using a combination of our remodeling model with the voxel finite element method. In this simulation, cancellous bone with randomly arranged trabeculae remodeled to form a well-organized architecture oriented parallel to the direction of loading, in agreement with the previous simulation results and experimental findings. These results suggested that our mathematical model for trabecular bone remodeling enables us to predict the reorganization of cancellous bone architecture from cellular activities. Furthermore, our remodeling model can represent the phenomenological law of bone transformation toward a locally uniform state of stress or strain at the trabecular level.

Keywords

Bone remodeling Cancellous bone Interstitial fluid flow Canaliculus Mathematical model Functional adaptation 

Notes

Acknowledgments

This study was partially supported by a Grant-in-Aid for Research Activity Start-up (23860044) and the Funding Program for Next Generation World-Leading Researchers (LR017) from the Japan Society for the Promotion of Science (JSPS).

References

  1. Adachi T, Tomita Y, Sakaue H, Tanaka M (1997) Simulation of trabecular surface remodeling based on local stress nonuniformity. JSME Int J 40C:782–792CrossRefGoogle Scholar
  2. Adachi T, Tsubota K, Tomita Y, Hollister SJ (2001) Trabecular surface remodeling simulation for cancellous bone using microstructural voxel finite element models. J Biomech Eng 123:403–409CrossRefGoogle Scholar
  3. Adachi T, Aonuma Y, Ito S, Tanaka M, Hojo M, Takano-Yamamoto T, Kamioka H (2009a) Osteocyte calcium signaling response to bone matrix deformation. J Biomech 42:2507–2512CrossRefGoogle Scholar
  4. Adachi T, Aonuma Y, Tanaka M, Hojo M, Takano-Yamamoto T, Kamioka H (2009b) Calcium response in single osteocytes to locally applied mechanical stimulus: differences in cell process and cell body. J Biomech 42:1989–1995CrossRefGoogle Scholar
  5. Adachi T, Aonuma Y, Taira K, Hojo M, Kamioka H (2009c) Asymmetric intercellular communication between bone cells: propagation of the calcium signaling. Biochem Biophys Res Commun 389:495–500CrossRefGoogle Scholar
  6. Adachi T, Kameo Y, Hojo M (2010) Trabecular bone remodeling simulation considering osteocytic response to fluid-induced shear stress. Philos Trans R Soc A 368:2669–2682CrossRefMATHMathSciNetGoogle Scholar
  7. Beno T, Yoon YJ, Cowin SC, Fritton SP (2006) Estimation of bone permeability using accurate microstructural measurements. J Biomech 39:2378–2387CrossRefGoogle Scholar
  8. Bonewald LF, Johnson ML (2008) Osteocytes, mechanosensing and Wnt signaling. Bone 42:606–615CrossRefGoogle Scholar
  9. Burger EH, Klein-Nulend J (1999) Mechanotransduction in bone—role of the lacuno-canalicular network. FASEB J 13:S101–S112Google Scholar
  10. Cowin SC, Moss-Salentijn L, Moss ML (1991) Candidates for the mechanosensory system in bone. J Biomech Eng 113:191–197CrossRefGoogle Scholar
  11. Cowin SC (1999) Bone poroelasticity. J Biomech 32:217–238CrossRefGoogle Scholar
  12. Fritton SP, Weinbaum S (2009) Fluid and solute transport in bone: flow-induced mechanotransduction. Annu Rev Fluid Mech 41:347–374CrossRefGoogle Scholar
  13. Gerhard FA, Webster DJ, van Lenthe GH, Muller R (2009) In silico biology of bone modelling and remodelling: adaptation. Philos Trans R Soc A 367:2011–2030CrossRefGoogle Scholar
  14. Goldstein SA, Matthews LS, Kuhn JL, Hollister SJ (1991) Trabecular bone remodeling: an experimental model. J Biomech 24:135–150CrossRefGoogle Scholar
  15. Guldberg RE, Caldwell NJ, Guo WE, Goulet RW, Hollister SJ, Goldstein SA (1997a) Mechanical stimulation of tissue repair in the hydraulic bone chamber. J Bone Miner Res 12:1295–1302CrossRefGoogle Scholar
  16. Guldberg RE, Richards M, Caldwell NJ, Kuelske CL, Goldstein SA (1997b) Trabecular bone adaptation to variations in porous-coated implant topology. J Biomech 30:147–153CrossRefGoogle Scholar
  17. Han Y, Cowin SC, Schaffler MB, Weinbaum S (2004) Mechanotransduction and strain amplification in osteocyte cell processes and flow across the endothelial glycocalyx. Proc Natl Acad Sci USA 101:16689–16694CrossRefGoogle Scholar
  18. Huiskes R, Weinans H, Grootenboer HJ, Dalstra M, Fudala B, Slooff TJ (1987) Adaptive bone-remodeling theory applied to prosthetic-design analysis. J Biomech 20:1135–1150CrossRefGoogle Scholar
  19. Huiskes R, Ruimerman R, Van Lenthe GH, Janssen JD (2000) Effects of mechanical forces on maintenance and adaptation of form in trabecular bone. Nature 405:704–706CrossRefGoogle Scholar
  20. Huo B, Lu XL, Hung CT, Costa KD, Xu Q, Whitesides GM, Guo XE (2008) Fluid flow induced calcium response in bone cell network. Cell Mol Bioeng 1:58–66CrossRefGoogle Scholar
  21. Jang IG, Kim IY (2008) Computational study of Wolff’s law with trabecular architecture in the human proximal femur using topology optimization. J Biomech 41:2353–2361CrossRefGoogle Scholar
  22. Jaworski ZF, Lok E (1972) The rate of osteoclastic bone erosion in haversian remodeling sites of adult dogs rib. Calcif Tissue Res 10:103–112CrossRefGoogle Scholar
  23. Kameo Y, Adachi T, Hojo M (2008) Transient response of fluid pressure in a poroelastic material under uniaxial cyclic loading. J Mech Phys Solids 56:1794–1805CrossRefMATHGoogle Scholar
  24. Kameo Y, Adachi T, Hojo M (2009) Fluid pressure response in poroelastic materials subjected to cyclic loading. J Mech Phys Solids 57:1815–1827CrossRefMATHMathSciNetGoogle Scholar
  25. Kameo Y, Adachi T, Hojo M (2010) Estimation of bone permeability considering the morphology of lacuno-canalicular porosity. J Mech Behav Biomed Mater 3:240–248CrossRefGoogle Scholar
  26. Kameo Y, Adachi T, Hojo M (2011) Effects of loading frequency on the functional adaptation of trabeculae predicted by bone remodeling simulation. J Mech Behav Biomed Mater 4:900–908CrossRefGoogle Scholar
  27. Kamioka H, Honjo T, Takano-Yamamoto T (2001) A three-dimensional distribution of osteocyte processes revealed by the combination of confocal laser scanning microscopy and differential interface contrast microscopy. Bone 28:145–149CrossRefGoogle Scholar
  28. Kamioka H, Murshid SA, Ishihara Y, Kajimura N, Hasegawa T, Ando R, Sugawara Y, Yamashiro T, Takaoka A, Takano-Yamamoto T (2009) A method for observing silver-stained osteocytes in situ in 3-\(\mu \)m sections using ultra-high voltage electron microscopy tomography. Microsc Microanal 15:377–383CrossRefGoogle Scholar
  29. Kamioka H, Kameo Y, Imai Y, Bakker AD, Bacabac RG, Yamada N, Takaoka A, Yamashiro T, Adachi T, Klein-Nulend J (2012) Microscale fluid flow analysis in human osteocyte canaliculus using a realistic high-resolution image-based three-dimensional model. Integr Biol 4:1198–1206CrossRefGoogle Scholar
  30. Knothe Tate ML, Knothe U, Niederer P (1998) Experimental elucidation of mechanical load-induced fluid flow and its potential role in bone metabolism and functional adaptation. Am J Med Sci 316: 189–195Google Scholar
  31. McNamara LM, Prendergast PJ (2007) Bone remodelling algorithms incorporating both strain and microdamage stimuli. J Biomech 40:1381–1391CrossRefGoogle Scholar
  32. Mullender MG, Huiskes R, Weinans H (1994) A physiological approach to the simulation of bone remodeling as a self-organizational control process. J Biomech 27:1389–1394CrossRefGoogle Scholar
  33. Mullender MG, Huiskes R (1995) Proposal for the regulatory mechanism of Wolff’s law. J Orthop Res 13:503–512CrossRefGoogle Scholar
  34. Mulvihill BM, Prendergast PJ (2008) An algorithm for bone mechanoresponsiveness: implementation to study the effect of patient-specific cell mechanosensitivity on trabecular bone loss. Comput Methods Biomech Biomed Eng 11:443–451CrossRefGoogle Scholar
  35. Nakashima T, Hayashi M, Fukunaga T, Kurata K, Oh-hora M, Feng JQ, Bonewald LF, Kodama T, Wutz A, Wagner EF, Penninger JM, Takayanagi H (2011) Evidence for osteocyte regulation of bone homeostasis through RANKL expression. Nat Med 17: 231–1234Google Scholar
  36. Osher S, Sethian JA (1988) Fronts propagating with curvature-dependent speed: algorithms based on Hamilton-Jacobi formulation. J Comput Phys 79:12–49CrossRefMATHMathSciNetGoogle Scholar
  37. Parfitt AM (1994) Osteonal and hemi-osteonal remodeling: the spatial and temporal framework for signal traffic in adult human bone. J Cell Biochem 55:273–286Google Scholar
  38. Prendergast PJ, Taylor D (1994) Prediction of bone adaptation using damage accumulation. J Biomech 27:1067–1076CrossRefGoogle Scholar
  39. Ruimerman R, Hilbers P, van Rietbergen B, Huiskes R (2005) A theoretical framework for strain-related trabecular bone maintenance and adaptation. J Biomech 38:931–941CrossRefGoogle Scholar
  40. Schulte FA, Ruffoni D, Lambers FM, Christen D, Webster DJ, Kuhn G, Muller R (2013) Local mechanical stimuli regulate bone formation and resorption in mice at the tissue level. Plos One 8:e62172CrossRefGoogle Scholar
  41. Smit TH, Huyghe JM, Cowin SC (2002) Estimation of the poroelastic parameters of cortical bone. J Biomech 35:829–835CrossRefGoogle Scholar
  42. Sugawara Y, Kamioka H, Honjo T, Tezuka K, Takano-Yamamoto T (2005) Three-dimensional reconstruction of chick calvarial osteocytes and their cell processes using confocal microscopy. Bone 36:877–883CrossRefGoogle Scholar
  43. Sugiyama T, Meakin LB, Browne WJ, Galea GL, Price JS, Lanyon LE (2012) Bones’ adaptive response to mechanical loading is essentially linear between the low strains associated with disuse and the high strains associated with the lamellar/woven bone transition. J Bone Miner Res 27:1784–1793CrossRefGoogle Scholar
  44. Tatsumi S, Ishii K, Amizuka N, Li MQ, Kobayashi T, Kohno K, Ito M, Takeshita S, Ikeda K (2007) Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab 5:464–475CrossRefGoogle Scholar
  45. Tsubota K, Adachi T, Tomita Y (2002) Functional adaptation of cancellous bone in human proximal femur predicted by trabecular surface remodeling simulation toward uniform stress state. J Biomech 35:1541–1551CrossRefGoogle Scholar
  46. Tsubota K, Adachi T (2004) Change in the fabric and compliance tensors of cancellous bone due to trabecular surface remodeling, predicted by a digital image-based model. Comput Methods Biomech Biomed Eng 7:187–192CrossRefGoogle Scholar
  47. Tsubota K, Adachi T (2005) Spatial and temporal regulation of cancellous bone structure: characterization of a rate equation of trabecular surface remodeling. Med Eng Phys 27:305–311CrossRefGoogle Scholar
  48. Tsubota K, Adachi T (2006) Computer simulation study on local and integral mechanical quantities at single trabecular level as candidates of remodeling stimuli. J Biomech Sci Eng 1:124–135CrossRefGoogle Scholar
  49. Tsubota K, Suzuki Y, Yamada T, Hojo M, Makinouchi A, Adachi T (2009) Computer simulation of trabecular remodeling in human proximal femur using large-scale voxel FE models: approach to understanding Wolff’s law. J Biomech 42:1088–1094CrossRefGoogle Scholar
  50. Wang Y, McNamara LM, Schaffler MB, Weinbaum S (2007) A model for the role of integrins in flow induced mechanotransduction in osteocytes. Proc Natl Acad Sci USA 104:15941–15946 Google Scholar
  51. Weinbaum S, Cowin SC, Zeng Y (1994) A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech 27:339–360Google Scholar
  52. Wolff J (1986) The law of bone remodeling. Springer, Berlin (translated by P. Maquet and R. Furlong)Google Scholar
  53. Wolff J (1892) Das gesetz der transformation der knochen. Hirschwald, BerlinGoogle Scholar
  54. You LD, Cowin SC, Schaffler MB, Weinbaum S (2001) A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J Biomech 34:1375–1386CrossRefGoogle Scholar
  55. You LD, Weinbaum S, Cowin SC, Schaffler MB (2004) Ultrastructure of the osteocyte process and its pericellular matrix. Anat Rec A 278A:505–513CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Mechanical Engineering, Graduate School of EngineeringOsaka Prefecture UniversityOsakaJapan
  2. 2.Department of Biomechanics, Research Center for Nano Medical Engineering, Institute for Frontier Medical SciencesKyoto UniversityKyotoJapan

Personalised recommendations