Real-time measurement of solute transport within the lacunar-canalicular system of mechanically loaded bone: Direct evidence for load-induced fluid flow

Abstract

Since proposed by Piekarski and Munro in 1977, load-induced fluid flow through the bone lacunar-canalicular system (LCS) has been accepted as critical for bone metabolism, mechanotransduction, and adaptation. However, direct unequivocal observation and quantification of load-induced fluid and solute convection through the LCS have been lacking due to technical difficulties. Using a novel experimental approach based on fluorescence recovery after photobleaching (FRAP) and synchronized mechanical loading and imaging, we successfully quantified the diffusive and convective transport of a small fluorescent tracer (sodium fluorescein, 376 Da) in the bone LCS of adult male C57BL/6J mice. We demonstrated that cyclic end-compression of the mouse tibia with a moderate loading magnitude (–3 N peak load or 400 µε surface strain at 0.5 Hz) and a 4-second rest/imaging window inserted between adjacent load cycles significantly enhanced (+31%) the transport of sodium fluorescein through the LCS compared with diffusion alone. Using an anatomically based three-compartment transport model, the peak canalicular fluid velocity in the loaded bone was predicted (60 µm/s), and the resulting peak shear stress at the osteocyte process membrane was estimated (∼5 Pa). This study convincingly demonstrated the presence of load-induced convection in mechanically loaded bone. The combined experimental and mathematical approach presented herein represents an important advance in quantifying the microfluidic environment experienced by osteocytes in situ and provides a foundation for further studying the mechanisms by which mechanical stimulation modulates osteocytic cellular responses, which will inform basic bone biology, clinical understanding of osteoporosis and bone loss, and the rational engineering of their treatments. © 2011 American Society for Bone and Mineral Research.

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References 38

1. 1.

   Bonewald LF. Osteocytes as dynamic multifunctional cells. Ann NY Acad Sci. 2007;1116:281-290.

   Not in our library10.1196/annals.1402.018

2. 2.

   Kogianni G, Noble BS. The biology of osteocytes. Curr Osteoporos Rep. 2007;5:81-86.

   Not in our library10.1007/s11914-007-0007-z

3. 3.

   Piekarski K, Munro M. Transport mechanism operating between blood supply and osteocytes in long bones. Nature. 1977;269:80-82.

   Not in our library10.1038/269080a0

4. 4.

   Hancox NM. Biology of Bone: Biological Structure and Function. 1972;viii.

   Not in our library

5. 5.

   You LD, Weinbaum S, Cowin SC, Schaffler MB. Ultrastructure of the osteocyte process and its pericellular matrix. Anat Rec A Discov Mol Cell Evol Biol. 2004;278:505-513.

   Not in our library10.1002/ar.a.20050

6. 6.

   Wang L, Wang Y, Han Y, et al. In situ measurement of solute transport in the bone lacunar-canalicular system. Proc Natl Acad Sci U S A. 2005;102:11911-11916.

   Not in our library10.1073/pnas.0505193102

7. 7.

   Cooper RR, Milgram JW, Robinson RA. Morphology of the osteon. An electron microscopic study. J Bone Joint Surg Am. 1966;48:1239-1271.

   Not in our library

8. 8.

   Riddle RC, Donahue HJ. From streaming-potentials to shear stress: 25 years of bone cell mechanotransduction. J Orthop Res. 2009;27:143-149.

   Not in our library10.1002/jor.20723

9. 9.

   Fritton SP, Weinbaum S. Fluid and Solute Transport in Bone: Flow-Induced Mechanotransduction. Ann Rev of Fluid Mechanics. 2009;41:347-374.

   Not in our library10.1146/annurev.fluid.010908.165136

10. 10.

    Kufahl RH, Saha S. A theoretical model for stress-generated fluid flow in the canaliculi-lacunae network in bone tissue. J Biomech. 1990;23:171-180.

    Not in our library10.1016/0021-9290(90)90350-c

11. 11.

    McCarthy ID, Yang L. A distributed model of exchange processes within the osteon. J Biomech. 1992;25:441-450.

    Not in our library10.1016/0021-9290(92)90263-z

12. 12.

    Weinbaum S, Cowin SC, Zeng Y. A model for the excitation of osteocytes by mechanical loading-induced bone fluid shear stresses. J Biomech. 1994;27:339-360.

    Not in our library10.1016/0021-9290(94)90010-8

13. 13.

    Steck R, Niederer P, Knothe Tate ML. A finite difference model of load-induced fluid displacements within bone under mechanical loading. Med Eng Phys. 2000;22:117-125.

    Not in our library10.1016/s1350-4533(00)00017-5

14. 14.

    Wang L, Cowin SC, Weinbaum S, Fritton SP. Modeling tracer transport in an osteon under cyclic loading. Ann Biomed Eng. 2000;28:1200-1209.

    Not in our library10.1114/1.1317531

15. 15.

    Gururaja S, Kim HJ, Swan CC, Brand RA, Lakes RS. Modeling deformation-induced fluid flow in cortical bone's canalicular-lacunar system. Ann Biomed Eng. 2005;33:7-25.

    Not in our library10.1007/s10439-005-8959-6

16. 16.

    Zhou X, Novotny JE, Wang L. Modeling fluorescence recovery after photobleaching in loaded bone: potential applications in measuring fluid and solute transport in the osteocytic lacunar-canalicular system. Ann Biomed Eng. 2008;36:1961-1977.

    Not in our library10.1007/s10439-008-9566-0

17. 17.

    Goulet GC, Coombe D, Martinuzzi RJ, Zernicke RF. Poroelastic evaluation of fluid movement through the lacunocanalicular system. Ann Biomed Eng. 2009;37:1390-1402.

    Not in our library10.1007/s10439-009-9706-1

18. 18.

    Knothe Tate ML, Knothe U, Niederer P. Experimental elucidation of mechanical load-induced fluid flow and its potential role in bone metabolism and functional adaptation. Am J Med Sci. 1998;316:189-195.

    Not in our library10.1097/00000441-199809000-00007

19. 19.

    Mak AF, Qin L, Hung LK, Cheng CW, Tin CF. A histomorphometric observation of flows in cortical bone under dynamic loading. Microvasc Res. 2000;59:290-300.

    Not in our library10.1006/mvre.1999.2215

20. 20.

    Knothe Tate ML, Steck R, Forwood MR, Niederer P. In vivo demonstration of load-induced fluid flow in the rat tibia and its potential implications for processes associated with functional adaptation. J Exp Biol. 2000;203:2737-2745.

    Not in our library10.1242/jeb.203.18.2737

21. 21.

    Zhou X, Novotny JE, Wang L. Anatomic variations of the lacunar-canalicular system influence solute transport in bone. Bone. 2009;45:704-710.

    Not in our library10.1016/j.bone.2009.06.026

22. 22.

    Wang L, Ciani C, Doty SB, Fritton SP. Delineating bone's interstitial fluid pathway in vivo. Bone. 2004;34:499-509.

    Not in our library10.1016/j.bone.2003.11.022

23. 23.

    Starkebaum W, Pollack SR, Korostoff E. Microelectrode studies of stress-generated potentials in four-point bending of bone. J Biomed Mater Res. 1979;13:729-751.

    Not in our library10.1002/jbm.820130506

24. 24.

    Otter MW, Palmieri VR, Wu DD, Seiz KG, MacGinitie LA, Cochran GV. A comparative analysis of streaming potentials in vivo and in vitro. J Orthop Res. 1992;10:710-719.

    Not in our library10.1002/jor.1100100513

25. 25.

    Qin YX, Lin W, Rubin C. The pathway of bone fluid flow as defined by in vivo intramedullary pressure and streaming potential measurements. Ann Biomed Eng. 2002;30:693-702.

    Not in our library10.1114/1.1483863

26. 26.

    Li W, You L, Schaffler MB, Wang L. The dependency of solute diffusion on molecular weight and shape in intact bone. Bone. 2009;45:1017-1023.

    Not in our library10.1016/j.bone.2009.07.076

27. 27.

    Price C, Li W, Novotny JE, Wang L. An in-situ fluorescence-based optical extensometry system for imaging mechanically loaded bone. J Orthop Res. 2010;28:805-811.

    Not in our library10.1002/jor.21049

28. 28.

    Gross TS, Poliachik SL, Ausk BJ, Sanford DA, Becker BA, Srinivasan S. Why rest stimulates bone formation: a hypothesis based on complex adaptive phenomenon. Exerc Sport Sci Rev. 2004;32:9-13.

    Not in our library10.1097/00003677-200401000-00003

29. 29.

    Fritton JC, Myers ER, Wright TM, van der Meulen MC. Loading induces site-specific increases in mineral content assessed by microcomputed tomography of the mouse tibia. Bone. 2005;36:1030-1038.

    Not in our library10.1016/j.bone.2005.02.013

30. 30.

    Marotti G, Muglia MA, Zaffe D. A SEM study of osteocyte orientation in alternately structured osteons. Bone. 1985;6:331-334.

    Not in our library10.1016/8756-3282(85)90324-2

31. 31.

    Cowin SC, Weinbaum S, Zeng Y. A case for bone canaliculi as the anatomical site of strain generated potentials. J Biomech. 1995;28:1281-1297.

    Not in our library10.1016/0021-9290(95)00058-p

32. 32.

    Su M, Jiang H, Zhang P, et al. Knee-loading modality drives molecular transport in mouse femur. Ann Biomed Eng. 2006;34:1600-1606.

    Not in our library10.1007/s10439-006-9171-z

33. 33.

    You L, Cowin SC, Schaffler MB, Weinbaum S. A model for strain amplification in the actin cytoskeleton of osteocytes due to fluid drag on pericellular matrix. J Biomech. 2001;34:1375-1386.

    Not in our library10.1016/s0021-9290(01)00107-5

34. 34.

    Han Y, Cowin SC, Schaffler MB, Weinbaum S. Mechanotransduction and strain amplification in osteocyte cell processes. Proc Natl Acad Sci U S A. 2004;101:16689-16694.

    Not in our library10.1073/pnas.0407429101

35. 35.

    Wang Y, McNamara LM, Schaffler MB, Weinbaum S. A model for the role of integrins in flow induced mechanotransduction in osteocytes. Proc Natl Acad Sci U S A. 2007;104:15941-15946.

    Not in our library10.1073/pnas.0707246104

36. 36.

    Longest PW, Kleinstreuer C, Deanda A. Numerical simulation of wall shear stress and particle-based hemodynamic parameters in pre-cuffed and streamlined end-to-side anastomoses. Ann Biomed Eng. 2005;33:1752-1766.

    Not in our library10.1007/s10439-005-7784-2

37. 37.

    Allen FD, Hung CT, Pollack SR, Brighton CT. Serum modulates the intracellular calcium response of primary cultured bone cells to shear flow. J Biomech. 2000;33:1585-1591.

    Not in our library10.1016/s0021-9290(00)00144-5

38. 38.

    Li W, Gardinier JD, Price C, Wang L. Does blood pressure enhance solute transport in the bone lacunar-canalicular system? Bone. 2010;47:353-359.

    Not in our library10.1016/j.bone.2010.05.005

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