This study describes the first application of a varus loading device (VLD) to the rat hind limb to study the role of sustained altered compressive loading and its relationship to the initiation of degenerative changes to the tibio-femoral joint. The VLD applies decreased compressive load to the lateral compartment and increased compressive load to the medial compartment of the tibio-femoral joint in a controlled manner. Mature rats were randomized into one of three groups: unoperated control, 0% (sham), or 80% body weight (BW). Devices were attached to an animal’s leg to deliver altered loads of 0% and 80% BW to the experimental knee for 12 weeks. Compartment-specific material properties of the tibial cartilage and subchondral bone were determined using indentation tests. Articular cartilage, calcified cartilage, and subchondral bone thicknesses, articular cartilage cellularity, and degeneration score were determined histologically. Joint tissues were sensitive to 12 weeks of decreased compressive loading in the lateral compartment with articular cartilage thickness decreased in the peripheral region, subchondral bone thickness increased, and cellularity of the midline region decreased in the 80% BW group as compared to the 0% BW group. The medial compartment revealed trends for diminished cellularity and aggregate modulus with increased loading. The rat-VLD model provides a new system to evaluate altered quantified levels of chronic in vivo loading without disruption of the joint capsule while maintaining full use of the knee. These results reveal a greater sensitivity of tissue parameters to decreased loading versus increased loading of 80% BW for 12 weeks in the rat. This model will allow future mechanistic studies that focus on the initiation and progression of degenerative changes with increased exposure in both magnitude and time to altered compressive loads.

References

References
1.
Brouwer
,
G. M.
,
Tol
,
A. W. V.
,
Bergink
,
A. P.
,
Belo
,
J. N.
,
Bernsen
,
R. M. D.
,
Reijman
,
M.
,
Pols
,
H. A. P.
, and
Bierma-Zeinstra
,
S. M. A.
, 2007, “
Association Between Valgus and Varus Alignment and the Development and Progression of Radiographic Osteoarthritis of the Knee
,”
Arthritis Rheum.
,
56
(
4
), pp.
1204
1211
.
2.
Felson
,
D. T.
,
Anderson
,
J. J.
,
Naimark
,
A.
,
Walker
,
A. M.
, and
Meenan
,
R. F.
, 1988, “
Obesity and Knee Osteoarthritis. The Framingham Study
,”
Ann. Intern. Med.
,
109
(
1
), pp.
18
24
.
3.
Segal
,
N. A.
,
Anderson
,
D. D.
,
Iyer
,
K. S.
,
Baker
,
J.
,
Torner
,
J. C.
,
Lynch
,
J. A.
,
Felson
,
D. T.
,
Lewis
,
C. E.
, and
Brown
,
T. D.
, 2009, “
Baseline Articular Contact Stress Levels Predict Incident Symptomatic Knee Osteoarthritis Development in the MOST Cohort
,”
J. Orthop. Res.
,
27
(
12
), pp.
1562
1568
.
4.
Buckwalter
,
J.
,
Mow
,
V.
, and
Ratcliffe
,
A.
, 1994, “
Restoration of Injured or Degenerated Articular Cartilage
,”
J. Am. Acad. Orthop. Surg.
,
2
(
4
), pp.
192
201
.
5.
Guilak
,
F.
, and
Hung
,
C. T.
, 2005, “
Physical Regulation of Cartilage Metabolism
,”
Basic Orthopaedic Biomechanics and Mechano-Biology
,
V. C.
Mow
and
R.
Huiskes
, eds.,
Lippincott Williams & Wilkins
,
Philadelphia
, pp.
259
300
.
6.
Carter
,
D. R.
,
Beaupre
,
G. S.
,
Wong
,
M.
,
Smith
,
R. L.
,
Andriacchi
,
T. P.
, and
Schurman
,
D. J.
, 2004, “
The Mechanobiology of Articular Cartilage Development and Degeneration
,”
Clin. Orthop. Relat. Res.
, (
427 Suppl
), pp.
S69
S77
.
7.
Gerwin
,
N.
,
Bendele
,
A. M.
,
Glasson
,
S.
, and
Carlson
,
C. S.
, 2010, “
The OARSI Histopathology Initiative—Recommendations for Histological Assessments of Osteoarthritis in the Rat
,”
Osteoarthritis Cartilage
,
18
(
Suppl 3
), pp.
S24
S34
.
8.
Roemhildt
,
M. L.
,
Coughlin
,
K. M.
,
Peura
,
G. D.
,
Badger
,
G. J.
,
Churchill
,
D.
,
Fleming
,
B. C.
, and
Beynnon
,
B. D.
, 2010, “
Effects of Increased Chronic Loading on Articular Cartilage Material Properties in the Lapine Tibio-Femoral Joint
,”
J. Biomech.
,
43
(
12
), pp.
2301
2308
.
9.
Roemhildt
,
M. L.
,
Fleming
,
B. C.
,
Beynnon
,
B. D.
, and
Churchill
,
D.
, 2009, “
101 In Vitro Validation of a Varus Loading Device in the Rabbit Knee
Osteoarthritis Cartilage
,
17
(Suppl
1
), p.
S62
.
10.
Roemhildt
,
M. L.
,
Beynnon
,
B. D.
,
Gardner-Morse
,
M.
,
Badger
,
G.
, and
Grant
,
C.
, 2012, “
Changes Induced by Chronic In Vivo Load Alteration in the Tibiofemoral Joint of Mature Rabbits
,”
J. Orthop. Res.
,
30
(
9
), pp.
1413
1422
.
11.
Roemhildt
,
M. L.
,
Gardner-Morse
,
M.
,
Rowell
,
C.
,
Beynnon
,
B. D.
, and
Badger
,
G. J.
, 2010, “
Gait Alterations in Rats Following Attachment of a Device and Application of Altered Knee Loading
,”
J. Biomech.
,
43
(
16
), pp.
3227
3231
.
12.
Mak
,
A. F.
,
Lai
,
W. M.
, and
Mow
,
V. C.
, 1987, “
Biphasic Indentation of Articular Cartilage–I. Theoretical Analysis
,”
J. Biomech.
,
20
(
7
), pp.
703
714
.
13.
Mow
,
V. C.
,
Gibbs
,
M. C.
,
Lai
,
W. M.
,
Zhu
,
W. B.
, and
Athanasiou
,
K. A.
, 1989, “
Biphasic Indentation of Articular Cartilage–II. A Numerical Algorithm and an Experimental Study
,”
J. Biomech.
,
22
(
8–9
), pp.
853
861
.
14.
Roemhildt
,
M. L.
,
Coughlin
,
K. M.
,
Peura
,
G. D.
,
Fleming
,
B. C.
, and
Beynnon
,
B. D.
, 2006, “
Material Properties of Articular Cartilage in the Rabbit Tibial Plateau
,”
J. Biomech.
,
39
(
12
), pp.
2331
2337
.
15.
Gardner-Morse
,
M. G.
,
Tacy
,
N. J.
,
Beynnon
,
B. D.
, and
Roemhildt
,
M. L.
, 2010, “
In Situ Microindentation for Determining Local Subchondral Bone Compressive Modulus
,”
J. Biomech. Eng.
,
132
(
9
), p.
094502
.
16.
Kiviranta
,
I.
,
Tammi
,
M.
,
Jurvelin
,
J.
,
Saamanen
,
A. M.
, and
Helminen
,
H. J.
, 1984, “
Fixation, Decalcification, and Tissue Processing Effects on Articular Cartilage Proteoglycans
,”
Histochemistry
,
80
(
6
), pp.
569
573
.
17.
Schmitz
,
N.
,
Laverty
,
S.
,
Kraus
,
V. B.
, and
Aigner
,
T.
, 2010, “
Basic Methods in Histopathology of Joint Tissues
,”
Osteoarthritis Cartilage
,
18
(
Suppl 3
), pp.
S113
S116
.
18.
Carmer
,
S. G.
, and
Swanson
,
S. A.
, 1973, “
An Evaluation of Ten Pairwise Multiple Comparisons Procedures by Monte Carlo Methods
,”
J. Am. Stat. Assoc.
,
68
(
341
), pp.
66
74
.
19.
O’Connor
,
K. M.
, 1997, “
Unweighting Accelerates Tidemark Advancement in Articular Cartilage at the Knee Joint of Rats
,”
J. Bone Miner. Res.
,
12
(
4
), pp.
580
589
.
20.
Wei
,
L.
,
Hjerpe
,
A.
,
Brismar
,
B. H.
, and
Svensson
,
O.
, 2001, “
Effect of Load on Articular Cartilage Matrix and the Development of Guinea-Pig Osteoarthritis
,”
Osteoarthritis Cartilage
,
9
(
5
), pp.
447
453
.
21.
Vanwanseele
,
B.
,
Eckstein
,
F.
,
Knecht
,
H.
,
Stüssi
,
E.
, and
Spaepen
,
A.
, 2002, “
Knee Cartilage of Spinal Cord–Injured Patients Displays Progressive Thinning in the Absence of Normal Joint Loading and Movement
,”
Arthritis Rheum.
,
46
(
8
), pp.
2073
2078
.
22.
Intema
,
F.
,
Van Roermund
,
P. M.
,
Marijnissen
,
A. C. A.
,
Cotofana
,
S.
,
Eckstein
,
F.
,
Castelein
,
R. M.
,
Bijlsma
,
J. W. J.
,
Mastbergen
,
S. C.
, and
Lafeber
,
F. P. J. G.
, 2011, “
Tissue Structure Modification in Knee Osteoarthritis by Use of Joint Distraction: An Open 1-Year Pilot Study
,”
Ann. Rheum. Dis.
,
70
(
8
), pp.
1441
1446
.
23.
Noyes
,
F. R.
,
Schipplein
,
O. D.
,
Andriachhi
,
T. P.
,
Saddemi
,
S. R.
, and
Weise
,
M.
, 1992, “
The Anterior Cruciate Ligament-Deficient Knee With Varus Alignment: An Analysis of Gait Adaptations and Dynamic Joint Loadings
,”
Am. J. Sports Med.
,
20
(
6
), pp.
707
716
.
24.
Roemhildt
,
M. L.
,
Anderson
,
K.
,
Beynnon
,
B. D.
, and
Gardner-Morse
,
M.
, 2010, “
235 Region Specific Cellularity of Articular Cartilage in the Tibial Plateau of the Mature Spague-Dawley Rat
,”
Osteoarthritis Cartilage
,
18
(
Suppl 2
), p.
S108
.
25.
Meachim
,
G.
, and
Collins
,
D. H.
, 1962, “
Cell Counts of Normal and Osteo-Arthritic Articular Cartilage in Relation to the Uptake of Sulphate (35SO4) In Vitro
,”
Ann. Rheum. Dis.
,
21
(
1
), pp.
45
50
.
26.
Vignon
,
E.
,
Arlot
,
M.
, and
Vignon
,
G.
, 1977, “
The Cellularity of Fibrillated Articular Cartilage. A Comparative Study of Age-Related and Osteoarthrotic Cartilage Lesions From the Human Femoral Head
,”
Pathol. Biol.
,
25
(
1
), pp.
29
32
.
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