Proteoglycans (PGs) are broadly distributed within many soft tissues and, among other roles, often contribute to mechanical properties. Although PGs, consisting of a core protein and glycosaminoglycan (GAG) sidechains, were once hypothesized to regulate stress/strain transfer between collagen fibrils and help support load in tendon, several studies have reported no changes to tensile mechanics after GAG depletion. Since GAGs are known to help sustain nontensile loading in other tissues, we hypothesized that GAGs might help support shear loading in human supraspinatus tendon (SST), a commonly injured tendon which functions in a complex multiaxial loading environment. Therefore, the objective of this study was to determine whether GAGs contribute to the response of SST to shear, specifically in terms of multiscale mechanical properties and mechanisms of microscale matrix deformation. Results showed that chondroitinase ABC (ChABC) treatment digested GAGs in SST while not disrupting collagen fibers. Peak and equilibrium shear stresses decreased only slightly after ChABC treatment and were not significantly different from pretreatment values. Reduced stress ratios were computed and shown to be slightly greater after ChABC treatment compared to phosphate-buffered saline (PBS) incubation without enzyme, suggesting that these relatively small changes in stress values were not due strictly to tissue swelling. Microscale deformations were also not different after ChABC treatment. This study demonstrates that GAGs possibly play a minor role in contributing to the mechanical behavior of SST in shear, but are not a key tissue constituent to regulate shear mechanics.

References

References
1.
September
,
A.
,
Rahim
,
M.
, and
Collins
,
M.
,
2016
, “
Towards an Understanding of the Genetics of Tendinopathy
,”
Metabolic Influences on Risk for Tendon Disorders
,
Springer
, New York, pp.
109
116
.
2.
Cook
,
J. L.
,
Rio
,
E.
,
Purdam
,
C. R.
, and
Docking
,
S. I.
,
2016
, “
Revisiting the Continuum Model of Tendon Pathology: What Is Its Merit in Clinical Practice and Research?
,”
Br. J. Sports Med.
,
50
(19), pp.
1187
1191
.
3.
Fang
,
F.
, and
Lake
,
S. P.
,
2016
, “
Modelling Approaches for Evaluating Multiscale Tendon Mechanics
,”
Interface Focus
,
6
(
1
), p. 20150044.
4.
Buckley
,
M. R.
,
Evans
,
E. B.
,
Matuszewski
,
P. E.
,
Chen
,
Y. L.
,
Satchel
,
L. N.
,
Elliott
,
D. M.
,
Soslowsky
,
L. J.
, and
Dodge
,
G. R.
,
2013
, “
Distributions of Types I, II and III Collagen by Region in the Human Supraspinatus Tendon
,”
Connect. Tissue Res.
,
54
(
6
), pp.
374
379
.
5.
Matuszewski
,
P. E.
,
Chen
,
Y. L.
,
Szczesny
,
S. E.
,
Lake
,
S. P.
,
Elliott
,
D. M.
,
Soslowsky
,
L. J.
, and
Dodge
,
G. R.
,
2012
, “
Regional Variation in Human Supraspinatus Tendon Proteoglycans: Decorin, Biglycan, and Aggrecan
,”
Connect. Tissue Res.
,
53
(
5
), pp.
343
348
.
6.
Fang
,
F.
, and
Lake
,
S. P.
,
2015
, “
Multiscale Strain Analysis of Tendon Subjected to Shear and Compression Demonstrates Strain Attenuation, Fiber Sliding, and Reorganization
,”
J. Orthop. Res.
,
33
(
11
), pp.
1704
1712
.
7.
Fang
,
F.
,
Sawhney
,
A. S.
, and
Lake
,
S. P.
,
2014
, “
Different Regions of Bovine Deep Digital Flexor Tendon Exhibit Distinct Elastic, But Not Viscous, Mechanical Properties Under Both Compression and Shear Loading
,”
J. Biomech.
,
47
(
12
), pp.
2869
2877
.
8.
Stubendorff
,
J. J.
,
Lammentausta
,
E.
,
Struglics
,
A.
,
Lindberg
,
L.
,
Heinegård
,
D.
, and
Dahlberg
,
L. E.
,
2012
, “
Is Cartilage sGAG Content Related to Early Changes in Cartilage Disease? Implications for Interpretation of dGEMRIC
,”
Osteoarthritis Cartilage
,
20
(
5
), pp.
396
404
.
9.
Fang
,
F.
, and
Lake
,
S. P.
,
2016
, “
Multiscale Mechanical Integrity of Human Supraspinatus Tendon in Shear After Elastin Depletion
,”
J. Mech. Behav. Biomed. Mater.
,
63
, pp.
443
455
.
10.
Choi
,
R. K.
,
Smith
,
M. M.
,
Martin
,
J. H.
,
Clarke
,
J. L.
,
Dart
,
A. J.
,
Little
,
C. B.
, and
Clarke
,
E. C.
,
2016
, “
Chondroitin Sulfate Glycosaminoglycans Contribute to Widespread Inferior Biomechanics in Tendon After Focal Injury
,”
J. Biomech.
,
49
(
13
), pp.
2694
2701
.
11.
Soslowsky
,
L. J.
,
Thomopoulos
,
S.
,
Tun
,
S.
,
Flanagan
,
C. L.
,
Keefer
,
C. C.
,
Mastaw
,
J.
, and
Carpenter
,
J. E.
,
2000
, “
Neer Award 1999: Overuse Activity Injures the Supraspinatus Tendon in an Animal Model: A Histologic and Biomechanical Study
,”
J. Shoulder Elbow Surg.
,
9
(
2
), pp.
79
84
.
12.
Henninger
,
H. B.
,
Underwood
,
C. J.
,
Ateshian
,
G. A.
, and
Weiss
,
J. A.
,
2010
, “
Effect of Sulfated Glycosaminoglycan Digestion on the Transverse Permeability of Medial Collateral Ligament
,”
J. Biomech.
,
43
(
13
), pp.
2567
2573
.
13.
Grant
,
T. M.
,
Yapp
,
C.
,
Chen
,
Q.
,
Czernuszka
,
J. T.
, and
Thompson
,
M. S.
,
2015
, “
The Mechanical, Structural, and Compositional Changes of Tendon Exposed to Elastase
,”
Ann. Biomed. Eng.
,
43
(
10
), pp.
2477
2486
.
14.
Dunkman
,
A. A.
,
Buckley
,
M. R.
,
Mienaltowski
,
M. J.
,
Adams
,
S. M.
,
Thomas
,
S. J.
,
Kumar
,
A.
,
Beason
,
D. P.
,
Iozzo
,
R. V.
,
Birk
,
D. E.
, and
Soslowsky
,
L. J.
,
2014
, “
The Injury Response of Aged Tendons in the Absence of Biglycan and Decorin
,”
Matrix Biol.
,
35
, pp.
232
238
.
15.
Dourte
,
L. M.
,
Pathmanathan
,
L.
,
Mienaltowski
,
M. J.
,
Jawad
,
A. F.
,
Birk
,
D. E.
, and
Soslowsky
,
L. J.
,
2013
, “
Mechanical, Compositional, and Structural Properties of the Mouse Patellar Tendon With Changes in Biglycan Gene Expression
,”
J. Orthop. Res.
,
31
(
9
), pp.
1430
1437
.
16.
Dourte
,
L. M.
,
Pathmanathan
,
L.
,
Jawad
,
A. F.
,
Iozzo
,
R. V.
,
Mienaltowski
,
M. J.
,
Birk
,
D. E.
, and
Soslowsky
,
L. J.
,
2012
, “
Influence of Decorin on the Mechanical, Compositional, and Structural Properties of the Mouse Patellar Tendon
,”
ASME J. Biomech. Eng.
,
134
(
3
), p.
031005
.
17.
Fang
,
F.
, and
Lake
,
S. P.
,
2017
, “
Experimental Evaluation of Multiscale Tendon Mechanics
,”
J. Orthop. Res.
, epub.
18.
Iozzo
,
R. V.
,
1997
, “
The Family of the Small Leucine-Rich Proteoglycans: Key Regulators of Matrix Assembly and Cellular Growth
,”
Crit. Rev. Biochem. Mol. Biol.
,
32
(
2
), pp.
141
174
.
19.
Landis
,
W. J.
, and
Silver
,
F. H.
,
2002
, “
The Structure and Function of Normally Mineralizing Avian Tendons
,”
Comp. Biochem. Physiol., Part A: Mol. Integr. Physiol.
,
133
(
4
), pp.
1135
1157
.
20.
Robbins
,
J. R.
,
Evanko
,
S. P.
, and
Vogel
,
K. G.
,
1997
, “
Mechanical Loading and TGF-β Regulate Proteoglycan Synthesis in Tendon
,”
Arch. Biochem. Biophys.
,
342
(
2
), pp.
203
211
.
21.
Feitosa
,
V. L. C.
,
Reis
,
F. P.
,
Esquisatto
,
M. A. M.
,
Joazeiro
,
P. P.
,
Vidal
,
B. C.
, and
Pimentel
,
E. R.
,
2006
, “
Comparative Ultrastructural Analysis of Different Regions of Two Digital Flexor Tendons of Pigs
,”
Micron
,
37
(
6
), pp.
518
525
.
22.
Nissi
,
M. J.
,
Salo
,
E. N.
,
Tiitu
,
V.
,
Liimatainen
,
T.
,
Michaeli
,
S.
,
Mangia
,
S.
,
Ellermann
,
J.
, and
Nieminen
,
M. T.
,
2015
, “
Multi-Parametric MRI Characterization of Enzymatically Degraded Articular Cartilage
,”
J. Orthop. Res.
,
34
(
7
), pp.
1111
1120
.
23.
Schmidt
,
M. B.
,
Mow
,
V. C.
,
Chun
,
L. E.
, and
Eyre
,
D. R.
,
1990
, “
Effects of Proteoglycan Extraction on the Tensile Behavior of Articular Cartilage
,”
J. Orthop. Res.
,
8
(
3
), pp.
353
363
.
24.
Soltz
,
M. A.
, and
Ateshian
,
G. A.
,
2000
, “
Interstitial Fluid Pressurization During Confined Compression Cyclical Loading of Articular Cartilage
,”
Ann. Biomed. Eng.
,
28
(
2
), pp.
150
159
.
25.
Wilusz
,
R. E.
,
Sanchez-Adams
,
J.
, and
Guilak
,
F.
,
2014
, “
The Structure and Function of the Pericellular Matrix of Articular Cartilage
,”
Matrix Biol.
,
39
, pp.
25
32
.
26.
Fessel
,
G.
, and
Snedeker
,
J. G.
,
2009
, “
Evidence Against Proteoglycan Mediated Collagen Fibril Load Transmission and Dynamic Viscoelasticity in Tendon
,”
Matrix Biol.
,
28
(
8
), pp.
503
510
.
27.
Fessel
,
G.
, and
Snedeker
,
J. G.
,
2011
, “
Equivalent Stiffness After Glycosaminoglycan Depletion in Tendon—An Ultra-Structural Finite Element Model and Corresponding Experiments
,”
J. Theor. Biol.
,
268
(
1
), pp.
77
83
.
28.
Lujan
,
T. J.
,
Underwood
,
C. J.
,
Henninger
,
H. B.
,
Thompson
,
B. M.
, and
Weiss
,
J. A.
,
2007
, “
Effect of Dermatan Sulfate Glycosaminoglycans on the Quasi‐Static Material Properties of the Human Medial Collateral Ligament
,”
J. Orthop. Res.
,
25
(
7
), pp.
894
903
.
29.
Svensson
,
R. B.
,
Hassenkam
,
T.
,
Hansen
,
P.
,
Kjaer
,
M.
, and
Magnusson
,
S. P.
,
2011
, “
Tensile Force Transmission in Human Patellar Tendon Fascicles Is Not Mediated by Glycosaminoglycans
,”
Connect. Tissue Res.
,
52
(
5
), pp.
415
421
.
30.
Gandley
,
R. E.
,
McLaughlin
,
M. K.
,
Koob
,
T. J.
,
Little
,
S. A.
, and
McGuffee
,
L. J.
,
1997
, “
Contribution of Chondroitin-Dermatan Sulfate-Containing Proteoglycans to the Function of Rat Mesenteric Arteries
,”
Am. J. Physiol.: Heart Circ. Physiol.
,
273
(
2
), pp.
H952
H960
.
31.
Mattson
,
J. M.
,
Turcotte
,
R.
, and
Zhang
,
Y.
,
2016
, “
Glycosaminoglycans Contribute to Extracellular Matrix Fiber Recruitment and Arterial Wall Mechanics
,”
Biomech. Model. Mechanobiol.
,
4
, pp.
1
13
.
32.
Deprés-Tremblay
,
G.
,
Chevrier
,
A.
,
Snow
,
M.
,
Hurtig
,
M. B.
,
Rodeo
,
S.
, and
Buschmann
,
M. D.
,
2016
, “
Rotator Cuff Repair: A Review of Surgical Techniques, Animal Models, and New Technologies Under Development
,”
J. Shoulder Elbow Surg.
,
25
(
12
), pp.
2078
2085
.
33.
Bey
,
M. J.
,
Ramsey
,
M. L.
, and
Soslowsky
,
L. J.
,
2002
, “
Intratendinous Strain Fields of the Supraspinatus Tendon: Effect of a Surgically Created Articular-Surface Rotator Cuff Tear
,”
J. Shoulder Elbow Surg.
,
11
(
6
), pp.
562
569
.
34.
Lake
,
S. P.
,
Miller
,
K. S.
,
Elliott
,
D. M.
, and
Soslowsky
,
L. J.
,
2009
, “
Effect of Fiber Distribution and Realignment on the Nonlinear and Inhomogeneous Mechanical Properties of Human Supraspinatus Tendon Under Longitudinal Tensile Loading
,”
J. Orthop. Res.
,
27
(
12
), pp.
1596
1602
.
35.
Lake
,
S. P.
,
Miller
,
K. S.
,
Elliott
,
D. M.
, and
Soslowsky
,
L. J.
,
2010
, “
Tensile Properties and Fiber Alignment of Human Supraspinatus Tendon in the Transverse Direction Demonstrate Inhomogeneity, Nonlinearity, and Regional Isotropy
,”
J. Biomech.
,
43
(
4
), pp.
727
732
.
36.
Zheng
,
C.
, and
Levenston
,
M. E.
,
2015
, “
Fact Versus Artifact: Avoiding Erroneous Estimates of Sulfated Glycosaminoglycan Content Using the Dimethylmethylene Blue Colorimetric Assay for Tissue-Engineered Constructs
,”
Eur. Cells Mater.
,
29
, pp.
224
236
.
37.
Koob
,
T. J.
, and
Vogel
,
K. G.
,
1987
, “
Site‐Related Variations in Glycosaminoglycan Content and Swelling Properties of Bovine Flexor Tendon
,”
J. Orthop. Res.
,
5
(
3
), pp.
414
424
.
38.
Grant
,
T. M.
,
Thompson
,
M. S.
,
Urban
,
J.
, and
Yu
,
J.
,
2013
, “
Elastic Fibres Are Broadly Distributed in Tendon and Highly Localized Around Tenocytes
,”
J. Anat.
,
222
(
6
), pp.
573
579
.
39.
Lujan
,
T. J.
,
Underwood
,
C. J.
,
Jacobs
,
N. T.
, and
Weiss
,
J. A.
,
2009
, “
Contribution of Glycosaminoglycans to Viscoelastic Tensile Behavior of Human Ligament
,”
J. Appl. Physiol.
,
106
(
2
), pp.
423
431
.
40.
Millesi
,
H.
,
Reihsner
,
R.
,
Hamilton
,
G.
,
Mallinger
,
R.
, and
Menzel
,
E. J.
,
1995
, “
Biomechanical Properties of Normal Tendons, Normal Palmar Aponeuroses, and Tissues From Patients With Dupuytren's Disease Subjected to Elastase and Chondroitinase Treatment
,”
Clin. Biomech.
,
10
(
1
), pp.
29
35
.
41.
Rigozzi
,
S.
,
Müller
,
R.
, and
Snedeker
,
J. G.
,
2009
, “
Local Strain Measurement Reveals a Varied Regional Dependence of Tensile Tendon Mechanics on Glycosaminoglycan Content
,”
J. Biomech.
,
42
(
10
), pp.
1547
1552
.
42.
Rigozzi
,
S.
,
Müller
,
R.
,
Stemmer
,
A.
, and
Snedeker
,
J. G.
,
2013
, “
Tendon Glycosaminoglycan Proteoglycan Sidechains Promote Collagen Fibril Sliding—AFM Observations at the Nanoscale
,”
J. Biomech.
,
46
(
4
), pp.
813
818
.
43.
Isaacs
,
J. L.
,
Vresilovic
,
E.
,
Sarkar
,
S.
, and
Marcolongo
,
M.
,
2014
, “
Role of Biomolecules on Annulus Fibrosus Micromechanics: Effect of Enzymatic Digestion on Elastic and Failure Properties
,”
J. Mech. Behav. Biomed. Mater.
,
40
, pp.
75
84
.
44.
Watanabe
,
T.
,
Kametani
,
K.
,
Koyama
,
Y.
,
Suzuki
,
D.
,
Imamura
,
Y.
,
Takehana
,
K.
, and
Hiramatsu
,
K.
,
2016
, “
Ring-Mesh Model of Proteoglycan Glycosaminoglycan Chains in Tendon Based on Three-Dimensional Reconstruction by Focused Ion Beam Scanning Electron Microscopy
,”
J. Biol. Chem.
,
291
(
45
), pp.
23704
23708
.
45.
Ahmadzadeh
,
H.
,
Connizzo
,
B. K.
,
Freedman
,
B. R.
,
Soslowsky
,
L. J.
, and
Shenoy
,
V. B.
,
2013
, “
Determining the Contribution of Glycosaminoglycans to Tendon Mechanical Properties With a Modified Shear-Lag Model
,”
J. Biomech.
,
46
(
14
), pp.
2497
2503
.
46.
Han
,
W. M.
,
Heo
,
S. J.
,
Driscoll
,
T. P.
,
Delucca
,
J. F.
,
McLeod
,
C. M.
,
Smith
,
L. J.
,
Duncan
,
R. L.
,
Mauck
,
R. L.
, and
Elliott
,
D. M.
,
2016
, “
Microstructural Heterogeneity Directs Micromechanics and Mechanobiology in Native and Engineered Fibrocartilage
,”
Nat. Mater.
,
15
(4), pp. 477–484.
47.
Gordon
,
J. A.
,
Freedman
,
B. R.
,
Zuskov
,
A.
,
Iozzo
,
R. V.
,
Birk
,
D. E.
, and
Soslowsky
,
L. J.
,
2015
, “
Achilles Tendons From Decorin-and Biglycan-Null Mouse Models Have Inferior Mechanical and Structural Properties Predicted by an Image-Based Empirical Damage Model
,”
J. Biomech.
,
48
(
10
), pp.
2110
2115
.
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