Bone adapts to habitual loading through mechanobiological signaling. Osteocytes are the primary mechanical sensors in bone, upregulating osteogenic factors and downregulating osteoinhibitors, and recruiting osteoclasts to resorb bone in response to microdamage accumulation. However, most of the cell populations of the bone marrow niche, which are intimately involved with bone remodeling as the source of bone osteoblast and osteoclast progenitors, are also mechanosensitive. We hypothesized that the deformation of trabecular bone would impart mechanical stress within the entrapped bone marrow consistent with mechanostimulation of the constituent cells. Detailed fluid-structure interaction models of porcine femoral trabecular bone and bone marrow were created using tetrahedral finite element meshes. The marrow was allowed to flow freely within the bone pores, while the bone was compressed to 2000 or 3000 microstrain at the apparent level. Marrow properties were parametrically varied from a constant 400 mPa·s to a power-law rule exceeding 85 Pa·s. Deformation generated almost no shear stress or pressure in the marrow for the low viscosity fluid, but exceeded 5 Pa when the higher viscosity models were used. The shear stress was higher when the strain rate increased and in higher volume fraction bone. The results demonstrate that cells within the trabecular bone marrow could be mechanically stimulated by bone deformation, depending on deformation rate, bone porosity, and bone marrow properties. Since the marrow contains many mechanosensitive cells, changes in the stimulatory levels may explain the alterations in bone marrow morphology with aging and disease, which may in turn affect the trabecular bone mechanobiology and adaptation.

References

References
1.
Schaffler
,
M. B.
,
Cheung
,
W. Y.
,
Majeska
,
R.
, and
Kennedy
,
O.
,
2014
, “
Osteocytes: Master Orchestrators of Bone
,”
Calcif. Tissue Int.
,
94
(
1
), pp.
5
24
.10.1007/s00223-013-9790-y
2.
Bonewald
,
L. F.
,
2011
, “
The Amazing Osteocyte
,”
J. Bone Miner. Res.
,
26
(
2
), pp.
229
238
.10.1002/jbmr.320
3.
Gurkan
,
U. A.
, and
Akkus
,
O.
,
2008
, “
The Mechanical Environment of Bone Marrow: A Review
,”
Ann. Biomed. Eng.
,
36
(
12
), pp.
1978
1991
.10.1007/s10439-008-9577-x
4.
Zhong
,
Z.
, and
Akkus
,
O.
,
2011
, “
Effects of Age and Shear Rate on the Rheological Properties of Human Yellow Bone Marrow
,”
Biorheology
,
48
(
2
), pp.
89
97
.10.3233/BIR-2011-0587
5.
Bryant
,
J. D.
,
David
,
T.
,
Gaskell
,
P. H.
,
King
,
S.
, and
Lond
,
G.
,
1989
, “
Rheology of Bovine Bone Marrow
,”
Proc. Inst. Mech. Eng., Part H
,
203
(
2
), pp.
71
75
.10.1243/PIME_PROC_1989_203_013_01
6.
Metzger
,
T. A.
,
Shudick
,
J. M.
,
Seekell
,
R.
,
Zhu
,
Y.
, and
Niebur
,
G. L.
,
2014
, “
Rheological Behavior of Fresh Bone Marrow and the Effects of Storage
,”
J. Mech. Behav. Biomed. Mater.
,
40
(
C
), pp.
307
313
.10.1016/j.jmbbm.2014.09.008
7.
Rosen
,
C. J.
, and
Bouxsein
,
M. L.
,
2006
, “
Mechanisms of Disease: Is Osteoporosis the Obesity of Bone?
,”
Nat. Clin. Pract. Rheumatol.
,
2
(
1
), pp.
35
43
.10.1038/ncprheum0070
8.
Devlin
,
M. J.
, and
Rosen
,
C. J.
, “
The Bone–Fat Interface: Basic and Clinical Implications of Marrow Adiposity
,”
Lancet Diabetes Endocrinol.
10.1016/S2213-8587(14)70007-5
9.
Gimble
,
J. M.
, and
Nuttall
,
M. E.
,
2012
, “
The Relationship Between Adipose Tissue and Bone Metabolism
,”
Clin. Biochem.
,
45
(
12
), pp.
874
879
.10.1016/j.clinbiochem.2012.03.006
10.
Kafka
,
V.
,
1993
, “
On Hydraulic Strengthening of Bones [Letter]
,”
J. Biomech.
,
26
(
6
), pp.
761
762
.10.1016/0021-9290(93)90038-G
11.
Bryant
,
J. D.
,
1988
, “
On the Mechanical Function of Marrow in Long Bones
,”
Eng. Med.
,
17
(
2
), pp.
55
58
.10.1243/EMED_JOUR_1988_017_017_02
12.
Bryant
,
J. D.
,
1983
, “
The Effect of Impact on the Marrow Pressure of Long Bones In Vitro
,”
J. Biomech.
,
16
(
8
), pp.
659
665
.10.1016/0021-9290(83)90117-3
13.
Ochoa
,
J. A.
,
Sanders
,
A. P.
,
Kiesler
,
T. W.
,
Heck
,
D. A.
,
Toombs
,
J. P.
,
Brandt
,
K. D.
, and
Hillberry
,
B. M.
,
1997
, “
In Vitro Observations of Hydraulic Stiffening in the Canine Femoral Head
,”
ASME J. Biomech. Eng.
,
119
(
1
), pp.
103
108
.10.1115/1.2796051
14.
Ochoa
,
J. A.
,
Sanders
,
A. P.
,
Heck
,
D. A.
, and
Hillberry
,
B. M.
,
1991
, “
Stiffening of the Femoral Head Due to Inter-Trabecular Fluid and Intraosseous Pressure
,”
ASME J. Biomech. Eng.
,
113
(
3
), pp.
259
262
.10.1115/1.2894882
15.
Pilcher
,
A.
,
Wang
,
X.
,
Kaltz
,
Z.
,
Garrison
,
J. G.
,
Niebur
,
G. L.
,
Mason
,
J.
,
Song
,
B.
,
Cheng
,
M.
, and
Chen
,
W.
,
2010
, “
High Strain Rate Testing of Bovine Trabecular Bone
,”
ASME J. Biomech. Eng.
,
132
(
8
), p.
081012
.10.1115/1.4000086
16.
Kasra
,
M.
, and
Grynpas
,
M. D.
,
2007
, “
On Shear Properties of Trabecular Bone Under Torsional Loading: Effects of Bone Marrow and Strain Rate
,”
J. Biomech.
,
40
(
13
), pp.
2898
2903
.10.1016/j.jbiomech.2007.03.008
17.
Carter
,
D. R.
, and
Hayes
,
W. C.
,
1976
, “
Bone Compressive Strength: The Influence of Density and Strain Rate
,”
Science
,
194
(
4270
), pp.
1174
1176
.10.1126/science.996549
18.
Arramon
,
Y. P.
, and
Cowin
,
S. C.
,
1997
, “
Hydraulic Stiffening of Cancellous Bone
,”
Forma
,
12
(
3,4
), pp.
209
221
.
19.
Whyne
,
C. M.
,
Hu
,
S. S.
, and
Lotz
,
J. C.
,
2001
, “
Parametric Finite Element Analysis of Vertebral Bodies Affected by Tumors
,”
J. Biomech.
,
34
(
10
), pp.
1317
1324
.10.1016/S0021-9290(01)00086-0
20.
Dickerson
,
D. A.
,
Sander
,
E. A.
, and
Nauman
,
E. A.
,
2008
, “
Modeling the Mechanical Consequences of Vibratory Loading in the Vertebral Body: Microscale Effects
,”
Biomech. Modell. Mechanobiol.
,
7
(
3
), pp.
191
202
.10.1007/s10237-007-0085-y
21.
Coughlin
,
T. R.
, and
Niebur
,
G. L.
,
2012
, “
Fluid Shear Stress in Trabecular Bone Marrow due to Low-Magnitude High-Frequency Vibration
,”
J. Biomech.
,
45
(
13
), pp.
2222
2229
.10.1016/j.jbiomech.2012.06.020
22.
Grellier
,
M.
,
Bareille
,
R.
,
Bourget
,
C.
, and
Amedee
,
J.
,
2009
, “
Responsiveness of Human Bone Marrow Stromal Cells to Shear Stress
,”
J. Tissue Eng. Regen. Med.
,
3
(
4
), pp.
302
309
.10.1002/term.166
23.
Miyanishi
,
K.
,
Trindade
,
M. C.
,
Lindsey
,
D. P.
,
Beaupre
,
G. S.
,
Carter
,
D. R.
,
Goodman
,
S. B.
,
Schurman
,
D. J.
, and
Smith
,
R. L.
,
2006
, “
Dose- and Time-Dependent Effects of Cyclic Hydrostatic Pressure on Transforming Growth Factor-Beta3-Induced Chondrogenesis by Adult Human Mesenchymal Stem Cells In Vitro
,”
Tissue Eng.
,
12
(
8
), pp.
2253
2262
.10.1089/ten.2006.12.2253
24.
Miyanishi
,
K.
,
Trindade
,
M. C.
,
Lindsey
,
D. P.
,
Beaupre
,
G. S.
,
Carter
,
D. R.
,
Goodman
,
S. B.
,
Schurman
,
D. J.
, and
Smith
,
R. L.
,
2006
, “
Effects of Hydrostatic Pressure and Transforming Growth Factor-Beta 3 on Adult Human Mesenchymal Stem Cell Chondrogenesis In Vitro
,”
Tissue Eng.
,
12
(
6
), pp.
1419
1428
.10.1089/ten.2006.12.1419
25.
Nagatomi
,
J.
,
Arulanandam
,
B. P.
,
Metzger
,
D. W.
,
Meunier
,
A.
, and
Bizios
,
R.
,
2003
, “
Cyclic Pressure Affects Osteoblast Functions Pertinent to Osteogenesis
,”
Ann. Biomed. Eng.
,
31
(
8
), pp.
917
923
.10.1114/1.1590663
26.
Nagatomi
,
J.
,
Arulanandam
,
B. P.
,
Metzger
,
D. W.
,
Meunier
,
A.
, and
Bizios
,
R.
,
2001
, “
Frequency- and Duration-Dependent Effects of Cyclic Pressure on Select Bone Cell Functions
,”
Tissue Eng.
,
7
(
6
), pp.
717
728
.10.1089/107632701753337672
27.
Qin
,
Y. X.
,
Kaplan
,
T.
,
Saldanha
,
A.
, and
Rubin
,
C.
,
2003
, “
Fluid Pressure Gradients, Arising From Oscillations in Intramedullary Pressure, Is Correlated With the Formation of Bone and Inhibition of Intracortical Porosity
,”
J. Biomech.
,
36
(
10
), pp.
1427
1437
.10.1016/S0021-9290(03)00127-1
28.
Rubin
,
J.
,
Biskobing
,
D.
,
Fan
,
X.
,
Rubin
,
C.
,
McLeod
,
K.
, and
Taylor
,
W. R.
,
1997
, “
Pressure Regulates Osteoclast Formation and MCSF Expression in Marrow Culture
,”
J. Cell Physiol.
,
170
(
1
), pp.
81
87
.10.1002/(SICI)1097-4652(199701)170:1<81::AID-JCP9>3.0.CO;2-H
29.
Nagatomi
,
J.
,
Arulanandam
,
B. P.
,
Metzger
,
D. W.
,
Meunier
,
A.
, and
Bizios
,
R.
,
2002
, “
Effects of Cyclic Pressure on Bone Marrow Cell Cultures
,”
ASME J. Biomech. Eng.
,
124
(
3
), pp.
308
314
.10.1115/1.1468867
30.
Birmingham
,
E.
,
Grogan
,
J. A.
,
Niebur
,
G. L.
,
McNamara
,
L. M.
, and
McHugh
,
P. E.
,
2013
, “
Computational Modelling of the Mechanics of Trabecular Bone and Marrow Using Fluid Structure Interaction Techniques
,”
Ann. Biomed. Eng.
,
41
(
4
), pp.
814
826
.10.1007/s10439-012-0714-1
31.
Gurkan
,
U. A.
,
Krueger
,
A.
, and
Akkus
,
O.
,
2011
, “
Ossifying Bone Marrow Explant Culture as a Three-Dimensional Mechanoresponsive In Vitro Model of Osteogenesis
,”
Tissue Eng, Part A
,
17
(
3–4
), pp.
417
428
.10.1089/ten.tea.2010.0193
32.
Gurkan
,
U. A.
,
Gargac
,
J.
, and
Akkus
,
O.
,
2010
, “
The Sequential Production Profiles of Growth Factors and Their Relations to Bone Volume in Ossifying Bone Marrow Explants
,”
Tissue Eng., Part A
,
16
(
7
), pp.
2295
2306
.10.1089/ten.tea.2009.0565
33.
Birmingham
,
E. C.
,
Kreipke
,
T. C.
,
Dolan
,
E. B.
,
Coughlin
,
T. R.
,
Owens
,
P.
,
McNamara
,
L. M.
,
Niebur
,
G. L.
, and
McHugh
,
P. E.
,
2014
, “
Mechanical Stimulation of Bone Marrow In Situ Induces Bone Formation in Trabecular Explants
,”
Ann. Biomed. Eng.
10.1007/s10439-014-1135-0
34.
Martin
,
R. B.
, and
Zissimos
,
S. L.
,
1991
, “
Relationships Between Marrow Fat and Bone Turnover in Ovariectomized and Intact Rats
,”
Bone
,
12
(
2
), pp.
123
131
.10.1016/8756-3282(91)90011-7
35.
Yeung
,
D. K.
,
Wong
,
S. Y.
,
Griffith
,
J. F.
, and
Lau
,
E. M.
,
2004
, “
Bone Marrow Diffusion in Osteoporosis: Evaluation With Quantitative MR Diffusion Imaging
,”
J. Magn. Reson. Imaging
,
19
(
2
), pp.
222
228
.10.1002/jmri.10453
36.
Griffith
,
J. F.
,
Yeung
,
D. K.
,
Tsang
,
P. H.
,
Choi
,
K. C.
,
Kwok
,
T. C.
,
Ahuja
,
A. T.
,
Leung
,
K. S.
, and
Leung
,
P. C.
,
2008
, “
Compromised Bone Marrow Perfusion in Osteoporosis
,”
J. Bone Miner. Res.
,
23
(
7
), pp.
1068
1075
.10.1359/jbmr.080233
37.
Devlin
,
M. J.
,
Cloutier
,
A. M.
,
Thomas
,
N. A.
,
Panus
,
D. A.
,
Lotinun
,
S.
,
Pinz
,
I.
,
Baron
,
R.
,
Rosen
,
C. J.
, and
Bouxsein
,
M. L.
,
2010
, “
Caloric Restriction Leads to High Marrow Adiposity and Low Bone Mass in Growing Mice
,”
J. Bone Miner. Res.
,
25
(
9
), pp.
2078
2088
.10.1002/jbmr.82
38.
Niebur
,
G. L.
,
Feldstein
,
M. J.
,
Yuen
,
J. C.
,
Chen
,
T. J.
, and
Keaveny
,
T. M.
,
2000
, “
High Resolution Finite Element Models With Tissue Strength Asymmetry Accurately Predict Failure of Trabecular Bone
,”
J. Biomech.
,
33
(
12
), pp.
1575
1583
.10.1016/S0021-9290(00)00149-4
39.
Bayraktar
,
H. H.
, and
Keaveny
,
T. M.
,
2004
, “
Mechanisms of Uniformity of Yield Strains for Trabecular Bone
,”
J. Biomech.
,
37
(
11
), pp.
1671
1678
.10.1016/j.jbiomech.2004.02.045
40.
Ochoa
,
J. A.
,
Heck
,
D. A.
,
Brandt
,
K. D.
, and
Hillberry
,
B. M.
,
1991
, “
The Effect of Intertrabecular Fluid on Femoral Head Mechanics
,”
J. Rheumatol.
,
18
(
4
), pp.
580
584
.
41.
Johnson
,
D. L.
,
McAllister
,
T. N.
, and
Frangos
,
J. A.
,
1996
, “
Fluid Flow Stimulates Rapid and Continuous Release of Nitric Oxide in Osteoblasts
,”
Am. J. Physiol.
,
271
(
1 Pt 1
), pp.
E205
E208
.
42.
McAllister
,
T. N.
, and
Frangos
,
J. A.
,
1999
, “
Steady and Transient Fluid Shear Stress Stimulate NO Release in Osteoblasts Through Distinct Biochemical Pathways
,”
J. Bone Miner. Res.
,
14
(
6
), pp.
930
936
.10.1359/jbmr.1999.14.6.930
43.
McAllister
,
T. N.
,
Du
,
T.
, and
Frangos
,
J. A.
,
2000
, “
Fluid Shear Stress Stimulates Prostaglandin and Nitric Oxide Release in Bone Marrow-Derived Preosteoclast-Like Cells
,”
Biochem. Biophys. Res. Commun.
,
270
(
2
), pp.
643
648
.10.1006/bbrc.2000.2467
44.
Castillo
,
A. B.
, and
Jacobs
,
C. R.
,
2010
, “
Mesenchymal Stem Cell Mechanobiology
,”
Curr. Osteoporosis Rep.
,
8
(
2
), pp.
98
104
.10.1007/s11914-010-0015-2
45.
Soves
,
C. P.
,
Miller
,
J. D.
,
Begun
,
D. L.
,
Taichman
,
R. S.
,
Hankenson
,
K. D.
, and
Goldstein
,
S. A.
,
2014
, “
Megakaryocytes are Mechanically Responsive and Influence Osteoblast Proliferation and Differentiation
,”
Bone
,
66
(
C
), pp.
111
120
.10.1016/j.bone.2014.05.015
46.
Liu
,
J.
,
Zhao
,
Z.
,
Li
,
J.
,
Zou
,
L.
,
Shuler
,
C.
,
Zou
,
Y.
,
Huang
,
X.
,
Li
,
M.
, and
Wang
,
J.
,
2009
, “
Hydrostatic Pressures Promote Initial Osteodifferentiation With ERK1/2 Not p38 MAPK Signaling Involved
,”
J. Cell. Biochem.
,
107
(
2
), pp.
224
232
.10.1002/jcb.22118
47.
Liu
,
J.
,
Zhao
,
Z.
,
Zou
,
L.
,
Li
,
J.
,
Wang
,
F.
,
Zhang
,
X.
,
Chen
,
S.
,
Zhi
,
M.
, and
Wang
,
J.
,
2009
, “
Pressure-Loaded MSCs During Early Osteodifferentiation Promote Osteoclastogenesis by Increase of RANKL/OPG Ratio
,”
Ann. Biomed. Eng.
,
37
(
4
), pp.
794
802
.10.1007/s10439-009-9638-9
48.
Frangos
,
J. A.
,
McIntire
,
L. V.
, and
Eskin
,
S. G.
,
1988
, “
Shear Stress Induced Stimulation of Mammalian Cell Metabolism
,”
Biotechnol. Bioeng.
,
32
(
8
), pp.
1053
1060
.10.1002/bit.260320812
49.
Sen
,
B.
,
Xie
,
Z.
,
Case
,
N.
,
Ma
,
M.
,
Rubin
,
C.
, and
Rubin
,
J.
,
2008
, “
Mechanical Strain Inhibits Adipogenesis in Mesenchymal Stem Cells by Stimulating a Durable Beta-Catenin Signal
,”
Endocrinology
,
149
(
12
), pp.
6065
6075
.10.1210/en.2008-0687
50.
Govey
,
P. M.
,
Loiselle
,
A. E.
, and
Donahue
,
H. J.
,
2013
, “
Biophysical Regulation of Stem Cell Differentiation
,”
Curr. Osteoporosis Rep.
,
11
(
2
), pp.
83
91
.10.1007/s11914-013-0138-3
51.
Harrigan
,
T. P.
,
Jasty
,
M.
,
Mann
,
R. W.
, and
Harris
,
W. H.
,
1988
, “
Limitations of the Continuum Assumption in Cancellous Bone
,”
J. Biomech.
,
21
(
4
), pp.
269
275
.10.1016/0021-9290(88)90257-6
52.
Bourne
,
B. C.
, and
van der Meulen
,
M. C. H.
,
2004
, “
Finite Element Models Predict Cancellous Apparent Modulus When Tissue Modulus is Scaled From Specimen CT-Attenuation
,”
J. Biomech.
,
37
(
5
), pp.
613
621
.10.1016/j.jbiomech.2003.10.002
53.
Jaasma
,
M. J.
,
Bayraktar
,
H. H.
,
Niebur
,
G. L.
, and
Keaveny
,
T. M.
,
2002
, “
Biomechanical Effects of Intraspecimen Variations in Tissue Modulus for Trabecular Bone
,”
J. Biomech.
,
35
(
2
), pp.
237
246
.10.1016/S0021-9290(01)00193-2
54.
Cowin
,
S. C.
,
1999
, “
Bone poroelasticity
,”
J. Biomech.
,
32
(
3
), pp.
217
238
.10.1016/S0021-9290(98)00161-4
55.
Cook
,
D.
,
Julias
,
M.
, and
Nauman
,
E.
,
2014
, “
Biological Variability in Biomechanical Engineering Research: Significance and Meta-Analysis of Current Modeling Practices
,”
J. Biomech.
,
47
(
6
), pp.
1241
1250
.10.1016/j.jbiomech.2014.01.040
56.
Yang
,
H.
,
Butz
,
K. D.
,
Duffy
,
D.
,
Niebur
,
G. L.
,
Nauman
,
E. A.
, and
Main
,
R. P.
,
2014
, “
Characterization of Cancellous and Cortical Bone Strain in the In Vitro Mouse Tibial Loading Model Using MicroCT-Based Finite Element Analysis
,”
Bone
,
66
, pp.
131
139
.10.1016/j.bone.2014.05.019
57.
Kohles
,
S. S.
,
Roberts
,
J. B.
,
Upton
,
M. L.
,
Wilson
,
C. G.
,
Bonassar
,
L. J.
, and
Schlichting
,
A. L.
,
2001
, “
Direct Perfusion Measurements of Cancellous Bone Anisotropic Permeability
,”
J. Biomech.
,
34
(
9
), pp.
1197
1202
.10.1016/S0021-9290(01)00082-3
58.
Souzanchi
,
M. F.
,
Cardoso
,
L.
, and
Cowin
,
S. C.
,
2013
, “
Tortuosity and the Averaging of Microvelocity Fields in Poroelasticity
,”
ASME J. Appl. Mech.
,
80
(
2
), p.
0209061
.10.1115/1.4007923
59.
Downey
,
D. J.
,
Simkin
,
P. A.
, and
Taggart
,
R.
,
1988
, “
The Effect of Compressive Loading on Intraosseous Pressure in the Femoral Head In Vitro
,”
J. Bone Joint Surg.
,
70
(
6
), pp.
871
877
.
60.
Mantila Roosa
,
S. M.
,
Liu
,
Y.
, and
Turner
,
C. H.
,
2011
, “
Gene Expression Patterns in Bone Following Mechanical Loading
,”
J. Bone Miner. Res.
,
26
(
1
), pp.
100
112
.10.1002/jbmr.193
61.
Shin
,
J. W.
,
Swift
,
J.
,
Ivanovska
,
I.
,
Spinler
,
K. R.
,
Buxboim
,
A.
, and
Discher
,
D. E.
,
2013
, “
Mechanobiology of Bone Marrow Stem Cells: From Myosin-II Forces to Compliance of Matrix and Nucleus in Cell Forms and Fates
,”
Differentiation
,
86
(
3
), pp.
77
86
.10.1016/j.diff.2013.05.001
62.
Wu
,
M. H.
,
Dimopoulos
,
G.
,
Mantalaris
,
A.
, and
Varley
,
J.
,
2004
, “
The Effect of Hyperosmotic Pressure on Antibody Production and Gene Expression in the GS-NS0 Cell Line
,”
Biotechnol. Appl. Biochem.
,
40
(Pt
1
), pp.
41
46
.10.1042/BA20030159
63.
Di Maggio
,
N.
,
Piccinini
,
E.
,
Jaworski
,
M.
,
Trumpp
,
A.
,
Wendt
,
D. J.
, and
Martin
,
I.
,
2011
, “
Toward Modeling the Bone Marrow Niche Using Scaffold-Based 3D Culture Systems
,”
Biomaterials
,
32
(
2
), pp.
321
329
.10.1016/j.biomaterials.2010.09.041
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