With the onset and progression of osteoarthritis (OA), articular cartilage (AC) mechanical properties are altered. These alterations can serve as an objective measure of tissue degradation. Although the mouse is a common and useful animal model for studying OA, it is extremely challenging to measure the mechanical properties of murine AC due to its small size (thickness < 50 μm). In this study, we developed novel and direct approach to independently quantify two quasi-static mechanical properties of mouse AC: the load-dependent (nonlinear) solid matrix Young's modulus (E) and drained Poisson's ratio (ν). The technique involves confocal microscope-based multiaxial strain mapping of compressed, intact murine AC followed by inverse finite element analysis (iFEA) to determine E and ν. Importantly, this approach yields estimates of E and ν that are independent of the initial guesses used for iterative optimization. As a proof of concept, mechanical properties of AC on the medial femoral condyles of wild-type mice were obtained for both trypsin-treated and control specimens. After proteolytic tissue degradation induced through trypsin treatment, a dramatic decrease in E was observed (compared to controls) at each of the three tested loading conditions. A significant decrease in ν due to trypsin digestion was also detected. These data indicate that the method developed in this study may serve as a valuable tool for comparative studies evaluating factors involved in OA pathogenesis using experimentally induced mouse OA models.

References

References
1.
Neogi
,
T.
,
2013
, “
The Epidemiology and Impact of Pain in Osteoarthritis
,”
Osteoarthritis Cartilage
,
21
(
9
), pp.
1145
1153
.
2.
Kleemann
,
R. U.
,
Krocker
,
D.
,
Cedraro
,
A.
,
Tuischer
,
J.
, and
Duda
,
G. N.
,
2005
, “
Altered Cartilage Mechanics and Histology in Knee Osteoarthritis: Relation to Clinical Assessment (ICRS Grade)
,”
Osteoarthritis Cartilage
,
13
(
11
), pp.
958
963
.
3.
Setton
,
L. A.
,
Elliott
,
D. M.
, and
Mow
,
V. C.
,
1999
, “
Altered Mechanics of Cartilage With Osteoarthritis: Human Osteoarthritis and an Experimental Model of Joint Degeneration
,”
Osteoarthritis Cartilage
,
7
(
1
), pp.
2
14
.
4.
Armstrong
,
C. G.
, and
Mow
,
V. C.
,
1982
, “
Variations in the Intrinsic Mechanical Properties of Human Articular Cartilage With Age, Degeneration, and Water Content
,”
J. Bone Jt. Surg. Am.
,
64
(
1
), pp.
88
94
.
5.
Wilusz
,
R. E.
,
Zauscher
,
S.
, and
Guilak
,
F.
,
2013
, “
Micromechanical Mapping of Early Osteoarthritic Changes in the Pericellular Matrix of Human Articular Cartilage
,”
Osteoarthritis Cartilage
,
21
(
12
), pp.
1895
1903
.
6.
Rivers
,
P. A.
,
Rosenwasser
,
M. P.
,
Mow
,
V. C.
,
Pawluk
,
R. J.
,
Strauch
,
R. J.
,
Sugalski
,
M. T.
, and
Ateshian
,
G. A.
,
2000
, “
Osteoarthritic Changes in the Biochemical Composition of Thumb Carpometacarpal Joint Cartilage and Correlation With Biomechanical Properties
,”
J. Hand Surg. Am.
,
25
(
5
), pp.
889
898
.
7.
Glasson
,
S. S.
,
Blanchet
,
T. J.
, and
Morris
,
E. A.
,
2007
, “
The Surgical Destabilization of the Medial Meniscus (DMM) Model of Osteoarthritis in the 129/SvEv Mouse
,”
Osteoarthritis Cartilage
,
15
(
9
), pp.
1061
1069
.
8.
Culley
,
K. L.
,
Dragomir
,
C. L.
,
Chang
,
J.
,
Wondimu
,
E. B.
,
Coico
,
J.
,
Plumb
,
D. A.
,
Otero
,
M.
, and
Goldring
,
M. B.
,
2015
, “
Mouse Models of Osteoarthritis: Surgical Model of Posttraumatic Osteoarthritis Induced by Destabilization of the Medial Meniscus
,”
Methods Mol. Biol.
,
1226
, pp.
143
173
.https://www.ncbi.nlm.nih.gov/pubmed/25331049
9.
David
,
M. A.
,
Smith
,
M. K.
,
Pilachowski
,
R. N.
,
White
,
A. T.
,
Locke
,
R. C.
, and
Price
,
C.
,
2016
, “
Early, Focal Changes in Cartilage Cellularity and Structure Following Surgically Induced Meniscal Destabilization in the Mouse
,”
J. Orthop. Res.
,
35
(
3
), pp.
537
547
.
10.
Kamekura
,
S.
,
Hoshi
,
K.
,
Shimoaka
,
T.
,
Chung
,
U.
,
Chikuda
,
H.
,
Yamada
,
T.
,
Uchida
,
M.
,
Ogata
,
N.
,
Seichi
,
A.
,
Nakamura
,
K.
, and
Kawaguchi
,
H.
,
2005
, “
Osteoarthritis Development in Novel Experimental Mouse Models Induced by Knee Joint Instability
,”
Osteoarthritis Cartilage
,
13
(
7
), pp.
632
641
.
11.
McNulty
,
M. A.
,
Loeser
,
R. F.
,
Davey
,
C.
,
Callahan
,
M. F.
,
Ferguson
,
C. M.
, and
Carlson
,
C. S.
,
2012
, “
Histopathology of Naturally Occurring and Surgically Induced Osteoarthritis in Mice
,”
Osteoarthritis Cartilage
,
20
(
8
), pp.
949
956
.
12.
Saamanen
,
A. K.
,
Salminen
,
H. J.
,
Dean
,
P. B.
,
De Crombrugghe
,
B.
,
Vuorio
,
E. I.
, and
Metsaranta
,
M. P.
,
2000
, “
Osteoarthritis-like Lesions in Transgenic Mice Harboring a Small Deletion Mutation in Type II Collagen Gene
,”
Osteoarthritis Cartilage
,
8
(
4
), pp.
248
257
.
13.
Xu
,
L.
,
Flahiff
,
C. M.
,
Waldman
,
B. A.
,
Wu
,
D.
,
Olsen
,
B. R.
,
Setton
,
L. A.
, and
Li
,
Y.
,
2003
, “
Osteoarthritis-like Changes and Decreased Mechanical Function of Articular Cartilage in the Joints of Mice With the Chondrodysplasia Gene (Cho)
,”
Arthritis Rheum.
,
48
(
9
), pp.
2509
2518
.
14.
Holt
,
D. W.
,
Henderson
,
M. L.
,
Stockdale
,
C. E.
,
Farrell
,
J. T.
,
Kooyman
,
D. L.
,
Bridgewater
,
L. C.
, and
Seegmiller
,
R. E.
,
2012
, “
Osteoarthritis-like Changes in the Heterozygous Sedc Mouse Associated With the HtrA1-Ddr2-Mmp-13 Degradative Pathway: A New Model of Osteoarthritis
,”
Osteoarthritis Cartilage
,
20
(
5
), pp.
430
439
.
15.
Cao
,
L.
,
Youn
,
I.
,
Guilak
,
F.
, and
Setton
,
L. A.
,
2006
, “
Compressive Properties of Mouse Articular Cartilage Determined in a Novel Micro-Indentation Test Method and Biphasic Finite Element Model
,”
ASME J. Biomech. Eng.
,
128
(
5
), pp.
766
771
.
16.
Berteau
,
J. P.
,
Oyen
,
M.
, and
Shefelbine
,
S. J.
,
2016
, “
Permeability and Shear Modulus of Articular Cartilage in Growing Mice
,”
Biomech. Model. Mechanobiol.
,
15
(
1
), pp.
205
212
.
17.
Batista
,
M. A.
,
Nia
,
H. T.
,
Onnerfjord
,
P.
,
Cox
,
K. A.
,
Ortiz
,
C.
,
Grodzinsky
,
A. J.
,
Heinegard
,
D.
, and
Han
,
L.
,
2014
, “
Nanomechanical Phenotype of Chondroadherin-Null Murine Articular Cartilage
,”
Matrix Biol.
,
38
, pp.
84
90
.
18.
Doyran
,
B.
,
Tong
,
W.
,
Li
,
Q.
,
Jia
,
H.
,
Zhang
,
X.
,
Chen
,
C.
,
Enomoto-Iwamoto
,
M.
,
Lu
,
X. L.
,
Qin
,
L.
, and
Han
,
L.
,
2016
, “
Nanoindentation Modulus of Murine Cartilage: A Sensitive Indicator of the Initiation and Progression of Post-Traumatic Osteoarthritis
,”
Osteoarthritis Cartilage
,
25
(
1
), pp.
108
117
.
19.
Azadi
,
M.
,
Nia
,
H. T.
,
Gauci
,
S. J.
,
Ortiz
,
C.
,
Fosang
,
A. J.
, and
Grodzinsky
,
A. J.
,
2016
, “
Wide Bandwidth Nanomechanical Assessment of Murine Cartilage Reveals Protection of Aggrecan Knock-In Mice From Joint-Overuse
,”
J. Biomech.
,
49
(
9
), pp.
1634
1640
.
20.
Nia
,
H. T.
,
Gauci
,
S. J.
,
Azadi
,
M.
,
Hung
,
H. H.
,
Frank
,
E.
,
Fosang
,
A. J.
,
Ortiz
,
C.
, and
Grodzinsky
,
A. J.
,
2015
, “
High-Bandwidth AFM-Based Rheology is a Sensitive Indicator of Early Cartilage Aggrecan Degradation Relevant to Mouse Models of Osteoarthritis
,”
J. Biomech.
,
48
(
1
), pp.
162
165
.
21.
Stolz
,
M.
,
Gottardi
,
R.
,
Raiteri
,
R.
,
Miot
,
S.
,
Martin
,
I.
,
Imer
,
R.
,
Staufer
,
U.
,
Raducanu
,
A.
,
Duggelin
,
M.
,
Baschong
,
W.
,
Daniels
,
A. U.
,
Friederich
,
N. F.
,
Aszodi
,
A.
, and
Aebi
,
U.
,
2009
, “
Early Detection of Aging Cartilage and Osteoarthritis in Mice and Patient Samples Using Atomic Force Microscopy
,”
Nat. Nanotechnol.
,
4
(
3
), pp.
186
192
.
22.
Moore
,
A. C.
,
DeLucca
,
J. F.
,
Elliott
,
D. M.
, and
Burris
,
D. L.
,
2016
, “
Quantifying Cartilage Contact Modulus, Tension Modulus, and Permeability With Hertzian Biphasic Creep
,”
ASME J. Tribol.
,
138
(
4
), p.
0414051
.
23.
Buckley
,
M. R.
,
Bonassar
,
L. J.
, and
Cohen
,
I.
,
2013
, “
Localization of Viscous Behavior and Shear Energy Dissipation in Articular Cartilage Under Dynamic Shear Loading
,”
ASME J. Biomech. Eng.
,
135
(
3
), p.
31002
.
24.
Henak
,
C. R.
,
Ross
,
K. A.
,
Bonnevie
,
E. D.
,
Fortier
,
L. A.
,
Cohen
,
I.
,
Kennedy
,
J. G.
, and
Bonassar
,
L. J.
,
2016
, “
Human Talar and Femoral Cartilage Have Distinct Mechanical Properties Near the Articular Surface
,”
J. Biomech.
,
49
(
14
), pp.
3320
3327
.
25.
Robinson
,
D. L.
,
Kersh
,
M. E.
,
Walsh
,
N. C.
,
Ackland
,
D. C.
,
de Steiger
,
R. N.
, and
Pandy
,
M. G.
,
2016
, “
Mechanical Properties of Normal and Osteoarthritic Human Articular Cartilage
,”
J. Mech. Behav. Biomed. Mater.
,
61
, pp.
96
109
.
26.
Silverberg
,
J. L.
,
Barrett
,
A. R.
,
Das
,
M.
,
Petersen
,
P. B.
,
Bonassar
,
L. J.
, and
Cohen
,
I.
,
2014
, “
Structure-Function Relations and Rigidity Percolation in the Shear Properties of Articular Cartilage
,”
Biophys. J.
,
107
(
7
), pp.
1721
1730
.
27.
Guterl
,
C. C.
,
Gardner
,
T. R.
,
Rajan
,
V.
,
Ahmad
,
C. S.
,
Hung
,
C. T.
, and
Ateshian
,
G. A.
,
2009
, “
Two-Dimensional Strain Fields on the Cross-Section of the Human Patellofemoral Joint Under Physiological Loading
,”
J. Biomech.
,
42
(
9
), pp.
1275
1281
.
28.
Park
,
S.
,
Costa
,
K. D.
,
Ateshian
,
G. A.
, and
Hong
,
K. S.
,
2009
, “
Mechanical Properties of Bovine Articular Cartilage Under Microscale Indentation Loading From Atomic Force Microscopy
,”
Proc. Inst. Mech. Eng., Part H
,
223
(
3
), pp.
339
347
.
29.
Chen
,
X.
,
Zhou
,
Y.
,
Wang
,
L.
,
Santare
,
M. H.
,
Wan
,
L. Q.
, and
Lu
,
X. L.
,
2016
, “
Determining Tension-Compression Nonlinear Mechanical Properties of Articular Cartilage From Indentation Testing
,”
Ann. Biomed. Eng.
,
44
(
4
), pp.
1148
1158
.
30.
Mow
,
V. C.
,
Kuei
,
S. C.
,
Lai
,
W. M.
, and
Armstrong
,
C. G.
,
1980
, “
Biphasic Creep and Stress Relaxation of Articular Cartilage in Compression? Theory and Experiments
,”
ASME J. Biomech. Eng.
,
102
(
1
), pp.
73
84
.
31.
Ateshian
,
G. A.
,
Warden
,
W. H.
,
Kim
,
J. J.
,
Grelsamer
,
R. P.
, and
Mow
,
V. C.
,
1997
, “
Finite Deformation Biphasic Material Properties of Bovine Articular Cartilage From Confined Compression Experiments
,”
J. Biomech.
,
30
(
11–12
), pp.
1157
1164
.
32.
Schinagl
,
R. M.
,
Gurskis
,
D.
,
Chen
,
A. C.
, and
Sah
,
R. L.
,
1997
, “
Depth-Dependent Confined Compression Modulus of Full-Thickness Bovine Articular Cartilage
,”
J. Orthop. Res.
,
15
(
4
), pp.
499
506
.
33.
Wong
,
B. L.
, and
Sah
,
R. L.
,
2010
, “
Mechanical Asymmetry During Articulation of Tibial and Femoral Cartilages: Local and Overall Compressive and Shear Deformation and Properties
,”
J. Biomech.
,
43
(
9
), pp.
1689
1695
.
34.
Han
,
L.
,
Frank
,
E. H.
,
Greene
,
J. J.
,
Lee
,
H. Y.
,
Hung
,
H. H.
,
Grodzinsky
,
A. J.
, and
Ortiz
,
C.
,
2011
, “
Time-Dependent Nanomechanics of Cartilage
,”
Biophys. J.
,
100
(
7
), pp.
1846
1854
.
35.
Elliott
,
D. M.
,
Narmoneva
,
D. A.
, and
Setton
,
L. A.
,
2002
, “
Direct Measurement of the Poisson's Ratio of Human Patella Cartilage in Tension
,”
ASME J. Biomech. Eng.
,
124
(
2
), pp.
223
228
.
36.
Griffin
,
D. J.
,
Vicari
,
J.
,
Buckley
,
M. R.
,
Silverberg
,
J. L.
,
Cohen
,
I.
, and
Bonassar
,
L. J.
,
2014
, “
Effects of Enzymatic Treatments on the Depth-Dependent Viscoelastic Shear Properties of Articular Cartilage
,”
J. Orthop. Res.
,
32
(
12
), pp.
1652
1657
.
37.
Chen
,
A. C.
,
Nguyen
,
T. T.
, and
Sah
,
R. L.
,
1997
, “
Streaming Potentials During the Confined Compression Creep Test of Normal and Proteoglycan-Depleted Cartilage
,”
Ann. Biomed. Eng.
,
25
(
2
), pp.
269
277
.
38.
Bonassar
,
L. J.
,
Frank
,
E. H.
,
Murray
,
J. C.
,
Paguio
,
C. G.
,
Moore
,
V. L.
,
Lark
,
M. W.
,
Sandy
,
J. D.
,
Wu
,
J. J.
,
Eyre
,
D. R.
, and
Grodzinsky
,
A. J.
,
1995
, “
Changes in Cartilage Composition and Physical Properties Due to Stromelysin Degradation
,”
Arthritis Rheum.
,
38
(
2
), pp.
173
183
.
39.
Armstrong
,
C. G.
,
Lai
,
W. M.
, and
Mow
,
V. C.
,
1984
, “
An Analysis of the Unconfined Compression of Articular Cartilage
,”
ASME J. Biomech. Eng.
,
106
(
2
), pp.
165
173
.
40.
Schneider
,
C. A.
,
Rasband
,
W. S.
, and
Eliceiri
,
K. W.
,
2012
, “
NIH Image to ImageJ: 25 Years of Image Analysis
,”
Nat. Methods
,
9
(
7
), pp.
671
675
.
41.
Maas
,
S. A.
,
Ellis
,
B. J.
,
Ateshian
,
G. A.
, and
Weiss
,
J. A.
,
2012
, “
FEBio: Finite Elements for Biomechanics
,”
ASME J. Biomech. Eng.
,
134
(
1
), p.
011005
.
42.
Wergedal
,
J. E.
,
Sheng
,
M. H.
,
Ackert-Bicknell
,
C. L.
,
Beamer
,
W. G.
, and
Baylink
,
D. J.
,
2005
, “
Genetic Variation in Femur Extrinsic Strength in 29 Different Inbred Strains of Mice is Dependent on Variations in Femur Cross-Sectional Geometry and Bone Density
,”
Bone
,
36
(
1
), pp.
111
122
.
43.
Madden
,
R.
,
Han
,
S. K.
, and
Herzog
,
W.
,
2013
, “
Chondrocyte Deformation Under Extreme Tissue Strain in Two Regions of the Rabbit Knee Joint
,”
J. Biomech.
,
46
(
3
), pp.
554
560
.
44.
Simon
,
W. H.
,
1970
, “
Scale Effects in Animal Joints—Part I: Articular Cartilage Thickness and Compressive Stress
,”
Arthritis Rheum.
,
13
(
3
), pp.
244
256
.
45.
Hughes
,
L. C.
,
Archer
,
C. W.
, and
ap Gwynn
,
I.
,
2005
, “
The Ultrastructure of Mouse Articular Cartilage: Collagen Orientation and Implications for Tissue Functionality. A Polarised Light and Scanning Electron Microscope Study and Review
,”
Eur. Cells Mater.
,
9
, pp.
68
84
.
46.
Glasson
,
S. S.
,
Chambers
,
M. G.
,
Van Den Berg
,
W. B.
, and
Little
,
C. B.
,
2010
, “
The OARSI Histopathology Initiative—Recommendations for Histological Assessments of Osteoarthritis in the Mouse
,”
Osteoarthritis Cartilage
,
18
(
Suppl. 3
), pp.
S17
S23
.
47.
Blaker
,
C. L.
,
Clarke
,
E. C.
, and
Little
,
C. B.
,
2017
, “
Using Mouse Models to Investigate the Pathophysiology, Treatment, and Prevention of Post-Traumatic Osteoarthritis
,”
J. Orthop. Res.
,
35
(
3
), pp.
537
547
.
You do not currently have access to this content.