Osteoarthritis (OA) is a degenerative joint disease that affects millions of people worldwide, yet its disease mechanism is not clearly understood. Animal models have been established to study disease progression by initiating OA through modified joint mechanics or altered biological activity within the joint. However, animal models often do not have the capability to directly relate the mechanical environment to joint damage. This review focuses on a novel in vivo approach based on controlled, cyclic tibial compression to induce OA in the mouse knee. First, we discuss the development of the load-induced OA model, its different loading configurations, and other techniques used by research laboratories around the world. Next, we review the lessons learned regarding the mechanobiological mechanisms of load-induced OA and relate these findings to the current understanding of the disease. Then, we discuss the role of specific genetic and cellular pathways involved in load-induced OA progression and the contribution of altered tissue properties to the joint response to mechanical loading. Finally, we propose using this approach to test the therapeutic efficacy of novel treatment strategies for OA. Ultimately, elucidating the mechanobiological mechanisms of load-induced OA will aid in developing targeted treatments for this disabling disease.
Issue Section:
Review Article
References
1.
Lawrence
, R. C.
, Felson
, D. T.
, Helmick
, C. G.
, Arnold
, L. M.
, Choi
, H.
, Deyo
, R. A.
, Gabriel
, S.
, Hirsch
, R.
, Hochberg
, M. C.
, Hunder
, G. G.
, Jordan
, J. M.
, Katz
, J. N.
, Kremers
, H. M.
, and Wolfe
, F.
, 2008
, “Estimates of the Prevalence of Arthritis and Other Rheumatic Conditions in the United States—Part II
,” Arthritis Rheumatol.
, 58
(1
), pp. 26
–35
.2.
Hootman
, J. M.
, and Helmick
, C. G.
, 2006
, “Projections of US Prevalence of Arthritis and Associated Activity Limitations
,” Arthritis Rheumatol.
, 54
(1
), pp. 226
–229
.3.
Felson
, D. T.
, 1988
, “Epidemiology of Hip and Knee Osteoarthritis
,” Epidemiol Rev.
, 10
, pp. 1
–28
.4.
Wieland
, H. A.
, Michaelis
, M.
, Kirschbaum
, B. J.
, and Rudolphi
, K. A.
, 2005
, “Osteoarthritis—An Untreatable Disease?
,” Nat. Rev. Drug Discov.
, 4
(4
), pp. 331
–344
.5.
Hunter
, D. J.
, and Felson
, D. T.
, 2006
, “Osteoarthritis
,” BMJ
, 332
(7542
), pp. 639
–642
.6.
Felson
, D. T.
, Anderson
, J. J.
, Naimark
, A.
, Walker
, A. M.
, and Meenan
, R. F.
, 1988
, “Obesity and Knee Osteoarthritis
,” Ann. Intern. Med.
, 109
(1
), p. 18
.7.
Messier
, S. P.
, Loeser
, R. F.
, Miller
, G. D.
, Morgan
, T. M.
, Rejeski
, W. J.
, Sevick
, M. A.
, Ettinger
, W. H.
, Pahor
, M.
, and Williamson
, J. D.
,. 2004
, “Exercise and Dietary Weight Loss in Overweight and Obese Older Adults With Knee Osteoarthritis: The Arthritis, Diet, and Activity Promotion Trial
,” Arthritis Rheumatol.
, 50
(5
), pp. 1501
–1510
.8.
Buckwalter
, J. A.
, Saltzman
, C.
, and Brown
, T.
, 2004
, “The Impact of Osteoarthritis: Implications for Research
,” Clin. Orthop. Relat. Res.
, 427
, pp. S6
–S15
.https://www.ncbi.nlm.nih.gov/pubmed/154800769.
Kaila-Kangas
, L.
, Arokoski
, J.
, Impivaara
, O.
, Viikari-Juntura
, E.
, Leino-Arjas
, P.
, Luukkonen
, R.
, and Heliövaara
, M.
, 2011
, “Associations of Hip Osteoarthritis With History of Recurrent Exposure to Manual Handling of Loads Over 20 kg and Work Participation: A Population-Based Study of Men and Women
,” Occup. Environ. Med.
, 68
(10
), pp. 734
–738
.10.
Cameron
, K. L.
, Hsiao
, M. S.
, Owens
, B. D.
, Burks
, R.
, and Svoboda
, S. J.
, 2011
, “Incidence of Physician-Diagnosed Osteoarthritis Among Active Duty United States Military Service Members
,” Arthritis Rheumatol.
, 63
(10
), pp. 2974
–2982
.11.
Felson
, D. T.
, Lawrence
, R. C.
, Dieppe
, P. A.
, Hirsch
, R.
, Helmick
, C. G.
, Jordan
, J. M.
, Kington
, R. S.
, Lane
, N. E.
, Nevitt
, M. C.
, Zhang
, Y.
, Sowers
, M.
, McAlindon
, T.
, Spector
, T. D.
, Poole
, A. R.
, Yanovski
, S. Z.
, Ateshian
, G.
, Sharma
, L.
, Buckwalter
, J. A.
, Brandt
, K. D.
, and Fries
, J. F.
, 2000
, “Osteoarthritis: New Insights—Part 1: The Disease and Its Risk Factors
,” Ann. Intern. Med.
, 133
(8
), p. 635
.12.
Lohmander
, L. S.
, Englund
, P. M.
, Dahl
, L. L.
, and Roos
, E. M.
, 2007
, “The Long-Term Consequence of Anterior Cruciate Ligament and Meniscus Injuries: Osteoarthritis
,” Am. J. Sports Med.
, 35
(10
), pp. 1756
–1769
.13.
Mobasheri
, A.
, Rayman
, M. P.
, Gualillo
, O.
, Sellam
, J.
, Van Der Kraan
, P.
, and Fearon
, U.
, 2017
, “The Role of Metabolism in the Pathogenesis of Osteoarthritis
,” Nat. Rev. Rheumatol.
, 13
(5
), pp. 302
–311
.14.
Arokoski
, J.
, Kiviranta
, I.
, Jurvelin
, J.
, Tammi
, M.
, and Helminen
, H. J.
, 1993
, “Long-Distance Running Causes Site-Dependent Decrease of Cartilage Glycosaminoglycan Content in the Knee Joints of Beagle Dogs
,” Arthritis Rheumatol.
, 36
(10
), pp. 1451
–1459
.15.
Lapveteläinen
, T.
, Nevalainen
, T.
, Parkkinen
, J. J.
, Arokoski
, J.
, Kiraly
, K.
, Hyttinen
, M.
, Halonen
, P.
, and Helminen
, H. J.
,. 1995
, “Lifelong Moderate Running Training Increases the Incidence and Severity of Osteoarthritis in the Knee Joint of C57BL Mice
,” Anat. Rec.
, 242
(2
), pp. 159
–165
.16.
Christiansen
, B. A.
, Guilak
, F.
, Lockwood
, K. A.
, Olson
, S. A.
, Pitsillides
, A. A.
, Sandell
, L. J.
, Silva
, M. J.
, van der Meulen
, M. C. H.
, and Haudenschild
, D. R.
, 2015
, “Non-Invasive Mouse Models of Post-Traumatic Osteoarthritis
,” Osteoarthritis Cartilage
, 23
(10
), pp. 1627
–1638
.17.
Holyoak
, D. T.
, Tian
, Y. F.
, van der Meulen
, M. C. H.
, and Singh
, A.
, 2016
, “Osteoarthritis: Pathology, Mouse Models, and Nanoparticle Injectable Systems for Targeted Treatment
,” Ann. Biomed. Eng.
, 44
(6
), pp. 2062
–2075
.18.
Bendele
, A. M.
, 2001
, “Animal Models of Osteoarthritis
,” J. Musculoskeletal Neuronal Interact.
, 1
(4
), pp. 363
–376
.http://www.ismni.org/jmni/pdf/4/bendeleOA.pdf19.
Poulet
, B.
, Hamilton
, R. W.
, Shefelbine
, S.
, and Pitsillides
, A. A.
, 2011
, “Characterizing a Novel and Adjustable Noninvasive Murine Joint Loading Model
,” Arthritis Rheumatol.
, 63
(1
), pp. 137
–147
.20.
Ko
, F. C.
, Dragomir
, C.
, Plumb
, D. A.
, Goldring
, S. R.
, Wright
, T. M.
, Goldring
, M. B.
, and van der Meulen
, M. C. H.
, 2013
, “In Vivo Cyclic Compression Causes Cartilage Degeneration and Subchondral Bone Changes in Mouse Tibiae
,” Arthritis Rheumatol.
, 65
(6
), pp. 1569
–1578
.21.
Bajpayee
, A. G.
, Scheu
, M.
, Grodzinsky
, A. J.
, and Porter
, R. M.
, 2015
, “A Rabbit Model Demonstrates the Influence of Cartilage Thickness on Intra-Articular Drug Delivery and Retention Within Cartilage
,” J. Orthop. Res.
, 33
(5
), pp. 660
–667
.22.
Gregory
, M. H.
, Capito
, N.
, Kuroki
, K.
, Stoker
, A. M.
, Cook
, J. L.
, and Sherman
, S. L.
, 2012
, “A Review of Translational Animal Models for Knee Osteoarthritis
,” Arthritis
, 2012
, p. 764621
.23.
van der Kraan
, P. M.
, Vitters
, E. L.
, van de Putte
, L. B.
, and van den Berg
, W. B.
, 1989
, “Development of Osteoarthritic Lesions in Mice by ‘Metabolic’ and ‘Mechanical’ Alterations in the Knee Joints
,” Am. J. Pathol.
, 135
(6
), pp. 1001
–1014
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1880494/24.
Kikuchi
, T.
, Sakuta
, T.
, and Yamaguchi
, T.
, 1998
, “Intra-Articular Injection of Collagenase Induces Experimental Osteoarthritis in Mature Rabbits
,” Osteoarthritis Cartilage
, 6
(3
), pp. 177
–186
.25.
van der Kraan
, P. M.
, Vitters
, E. L.
, van Beuningen
, H. M.
, van de Putte
, L. B.
, and van den Berg
, W. B.
, 1990
, “Degenerative Knee Joint Lesions in Mice After a Single Intra-Articular Collagenase Injection: A New Model of Osteoarthritis
,” J. Exp. Pathol. (Oxford)
, 71
(1
), pp. 19
–31
.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1998679/26.
van Beuningen
, H.
, Glansbeek
, H.
, van der Kraan
, P.
, and van den Berg
, W.
, 2000
, “Osteoarthritis-Like Changes in the Murine Knee Joint Resulting From Intra-Articular Transforming Growth Factor-β Injections
,” Osteoarthritis Cartilage
, 8
(1
), pp. 25
–33
.27.
Clements
, K. M.
, Ball
, A. D.
, Jones
, H. B.
, Brinckmann
, S.
, Read
, S. J.
, and Murray
, F.
, 2009
, “Cellular and Histopathological Changes in the Infrapatellar Fat Pad in the Monoiodoacetate Model of Osteoarthritis Pain
,” Osteoarthritis Cartilage
, 17
(6
), pp. 805
–812
.28.
Guzman
, R. E.
, Evans
, M. G.
, Bove
, S.
, Morenko
, B.
, and Kilgore
, K.
, 2003
, “Mono-Iodoacetate-Induced Histologic Changes in Subchondral Bone and Articular Cartilage of Rat Femorotibial Joints: An Animal Model of Osteoarthritis
,” Toxicol. Pathol.
, 31
(6
), pp. 619
–624
.29.
Bove
, S. E.
, Calcaterra
, S. L.
, Brooker
, R. M.
, Huber
, C. M.
, Guzman
, R. E.
, Juneau
, P. L.
, Schrier
, D. J.
, and Kilgore
, K. S.
,. 2003
, “Weight Bearing as a Measure of Disease Progression and Efficacy of Anti-Inflammatory Compounds in a Model of Monosodium Iodoacetate-Induced Osteoarthritis
,” Osteoarthritis Cartilage
, 11
(11
), pp. 821
–830
.30.
Combe
, R.
, Bramwell
, S.
, and Field
, M. J.
, 2004
, “The Monosodium Iodoacetate Model of Osteoarthritis: A Model of Chronic Nociceptive Pain in Rats?
,” Neurosci. Lett.
, 370
(2–3
), pp. 236
–240
.31.
Little
, C. B.
, and Zaki
, S.
, 2012
, “What Constitutes an “Animal Model of Osteoarthritis”—The Need for Consensus?
,” Osteoarthritis Cartilage
, 20
(4
), pp. 261
–267
.32.
Inoue
, S.
, and Glimcher
, M. J.
, 1982
, “The Reaction of Cartilage and Osteophyte Formation After the Intraarticular Injection of Papain
,” Nihon Seikeigeka Gakkai Zasshi
, 56
(5
), pp. 415
–430
.https://www.ncbi.nlm.nih.gov/pubmed/710832033.
Murat
, N.
, Karadam
, B.
, Ozkal
, S.
, Karatosun
, V.
, and Gidener
, S.
, 2007
, “Quantification of Papain-Induced Rat Osteoarthritis in Relation to Time With the Mankin Score
,” Acta Orthop. Traumatol. Turc.
, 41
(3
), pp. 233
–237
.https://www.ncbi.nlm.nih.gov/pubmed/1787612534.
Bentley
, G.
, 1971
, “Papain-Induced Degenerative Arthritis of the Hip in Rabbits
,” J. Bone Jt. Surg. Br.
, 53
(2
), pp. 324
–337
.https://www.ncbi.nlm.nih.gov/pubmed/557822735.
Pond
, M. J.
, and Nuki
, G.
, 1973
, “Experimentally-Induced Osteoarthritis in the Dog
,” Ann. Rheumatol. Dis.
, 32
(4
), pp. 387
–388
.36.
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
.37.
Hayami
, T.
, Pickarski
, M.
, Zhuo
, Y.
, Wesolowski
, G. A.
, Rodan
, G. A.
, and Duong
, L. T.
, 2006
, “Characterization of Articular Cartilage and Subchondral Bone Changes in the Rat Anterior Cruciate Ligament Transection and Meniscectomized Models of Osteoarthritis
,” Bone
, 38
(2
), pp. 234
–243
.38.
McErlain
, D. D.
, Appleton
, C. T. G.
, Litchfield
, R. B.
, Pitelka
, V.
, Henry
, J. L.
, Bernier
, S. M.
, Beier
, F.
, and Holdsworth
, D. W.
, 2008
, “Study of Subchondral Bone Adaptations in a Rodent Surgical Model of OA Using In Vivo Micro-Computed Tomography
,” Osteoarthritis Cartilage
, 16
(4
), pp. 458
–469
.39.
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
.40.
Culley
, K. L.
, Dragomir
, C. L.
, and Chang
, J.
, 2015
, Mouse Models of Osteoarthritis: Surgical Model of Posttraumatic Osteoarthritis Induced by Destabilization of the Medial Meniscus
, Humana Press
, New York
, pp. 143
–173
.41.
Poulet
, B.
, 2016
, “Non-Invasive Loading Model of Murine Osteoarthritis
,” Curr. Rheumatol. Rep.
, 18
(7
), p. 40
.42.
McCoy
, A. M.
, 2015
, “Animal Models of Osteoarthritis: Comparisons and Key Considerations
,” Vet. Pathol.
, 52
(5
), pp. 803
–818
.43.
Jimenez
, P. A.
, Glasson
, S. S.
, Trubetskoy
, O. V.
, and Haimes
, H. B.
, 1997
, “Spontaneous Osteoarthritis in Dunkin Hartley guinea Pigs: Histologic, Radiologic, and Biochemical Changes
,” Lab Anim. Sci.
, 47
(6
), pp. 598
–601
.https://www.ncbi.nlm.nih.gov/pubmed/943369544.
Furman
, B. D.
, Strand
, J.
, Hembree
, W. C.
, Ward
, B. D.
, Guilak
, F.
, and Olson
, S. A.
, 2007
, “Joint Degeneration Following Closed Intraarticular Fracture in the Mouse Knee: A Model of Posttraumatic Arthritis
,” J. Orthop. Res.
, 25
(5
), pp. 578
–592
.45.
Lewis
, J. S.
, Hembree
, W. C.
, Furman
, B. D.
, Tippets
, L.
, Cattel
, D.
, Huebner
, J. L.
, Little
, D.
, DeFrate
, L. E.
, Kraus
, V. B.
, Guilak
, F.
, and Olson
, S. A.
, 2011
, “Acute Joint Pathology and Synovial Inflammation is Associated With Increased Intra-Articular Fracture Severity in the Mouse Knee
,” Osteoarthritis Cartilage
, 19
(7
), pp. 864
–873
.46.
Christiansen
, B. A.
, Anderson
, M. J.
, Lee
, C. A.
, Williams
, J. C.
, Yik
, J. H. N.
, and Haudenschild
, D. R.
, 2012
, “Musculoskeletal Changes Following Non-Invasive Knee Injury Using a Novel Mouse Model of Post-Traumatic Osteoarthritis
,” Osteoarthritis Cartilage
, 20
(7
), pp. 773
–782
.47.
Wu
, P.
, Holguin
, N.
, Silva
, M. J.
, Fu
, M.
, Liao
, W.
, and Sandell
, L. J.
, 2014
, “Early Response of Mouse Joint Tissue to Noninvasive Knee Injury Suggests Treatment Targets
,” Arthritis Rheumatol.
, 66
(5
), pp. 1256
–1265
.48.
Stoop
, R.
, van der Kraan
, P. M.
, Buma
, P.
, Hollander
, A. P.
, Billinghurst
, R. C.
, Poole
, A. R.
, and van den Berg
, W. B.
, 1999
, “Type II Collagen Degradation in Spontaneous Osteoarthritis in C57BL/6 and BALB/c Mice
,” Arthritis Rheumatol.
, 42
(11
), pp. 2381
–2389
.49.
Esapa
, C. T.
, Hough
, T. A.
, Testori
, S.
, Head
, R. A.
, Crane
, E. A.
, Chan
, C. P.
, Evans
, H.
, Bassett
, J. D.
, Tylzanowski
, P.
, McNally
, E. G.
, Carr
, A. J.
, Boyde
, A.
, Howell
, P. G.
, Clark
, A.
, Williams
, G. R.
, Brown
, M. A.
, Croucher
, P. I.
, Nesbit
, M. A.
, Brown
, S. D.
, Cox
, R. D.
, Cheeseman
, M. T.
, and Thakker
, R. V.
, 2012
, “A Mouse Model for Spondyloepiphyseal Dysplasia Congenita With Secondary Osteoarthritis Due to a Col2a1 Mutation
,” J. Bone Miner. Res.
, 27
(2
), pp. 413
–428
.50.
Vasheghani
, F.
, Zhang
, Y.
, Li
, Y.-H.
, Blati
, M.
, Fahmi
, H.
, Lussier
, B.
, Roughley
, P.
, Lagares
, D.
, Endisha
, H.
, Saffar
, B.
, Lajeunesse
, D.
, Marshall
, W. K.
, Rampersaud
, Y. R.
, Mahomed
, N. N.
, Gandhi
, R.
, Pelletier
, J.-P.
, Martel-Pelletier
, J.
, and Kapoor
, M.
, 2015
, “PPARγ Deficiency Results in Severe, Accelerated Osteoarthritis Associated With Aberrant mTOR Signalling in the Articular Cartilage
,” Ann. Rheumatol. Dis.
, 74
(3
), pp. 569
–578
.51.
Fritton
, J. C.
, Myers
, E. R.
, Wright
, T. M.
, and Van Der Meulen
, M.
, 2005
, “Loading Induces Site-Specific Increases in Mineral Content Assessed by Microcomputed Tomography of the Mouse Tibia
,” Bone
, 36
(6
), pp. 1030
–1038
.52.
De Souza
, R. L.
, Matsuura
, M.
, Eckstein
, F.
, Rawlinson
, S. C. F.
, Lanyon
, L. E.
, and Pitsillides
, A. A.
, 2005
, “Non-Invasive Axial Loading of Mouse Tibiae Increases Cortical Bone Formation and Modifies Trabecular Organization: A New Model to Study Cortical and Cancellous Compartments in a Single Loaded Element
,” Bone
, 37
(6
), pp. 810
–818
.53.
Lee
, K.
, Maxwell
, A.
, and Lanyon
, L.
, 2002
, “Validation of a Technique for Studying Functional Adaptation of the Mouse Ulna in Response to Mechanical Loading
,” Bone
, 31
(3
), pp. 407
–412
.54.
Lynch
, M. E.
, Main
, R. P.
, Xu
, Q.
, Schmicker
, T. L.
, Schaffler
, M. B.
, Wright
, T. M.
, and van der Meulen
, M. C. H.
, 2011
, “Tibial Compression is Anabolic in the Adult Mouse Skeleton Despite Reduced Responsiveness With Aging
,” Bone
, 49
(3
), pp. 439
–446
.55.
Sugiyama
, T.
, Saxon
, L. K.
, Zaman
, G.
, Moustafa
, A.
, Sunters
, A.
, Price
, J. S.
, and Lanyon
, L. E.
, 2008
, “Mechanical Loading Enhances the Anabolic Effects of Intermittent Parathyroid Hormone (1–34) on Trabecular and Cortical Bone in Mice
,” Bone
, 43
(2
), pp. 238
–248
.56.
Melville
, K. M.
, Robling
, A. G.
, and van der Meulen
, M.
, 2015
, “In Vivo Axial Loading of the Mouse Tibia
,” Methods Mol. Biol.
, 1226
, pp. 99
–115
.57.
Mosley
, J. R.
, March
, B. M.
, Lynch
, J.
, and Lanyon
, L. E.
, 1997
, “Strain Magnitude Related Changes in Whole Bone Architecture in Growing Rats
,” Bone
, 20
(3
), pp. 191
–198
.58.
Rubin
, C. T.
, and Lanyon
, L. E.
, 1985
, “Regulation of Bone Mass by Mechanical Strain Magnitude
,” Calcif. Tissue Int.
, 37
(4
), pp. 411
–417
.59.
Poulet
, B.
, de Souza
, R.
, Kent
, A. V.
, Saxon
, L.
, Barker
, O.
, Wilson
, A.
, Chang
, Y.-M.
, Cake
, M.
, and Pitsillides
, A. A.
, 2015
, “Intermittent Applied Mechanical Loading Induces Subchondral Bone Thickening That May Be Intensified Locally by Contiguous Articular Cartilage Lesions
,” Osteoarthritis Cartilage
, 23
(6
), pp. 940
–948
.60.
Astephen Wilson
, J. L.
, Deluzio
, K. J.
, Dunbar
, M. J.
, Caldwell
, G. E.
, and Hubley-Kozey
, C. L.
, 2011
, “The Association Between Knee Joint Biomechanics and Neuromuscular Control and Moderate Knee Osteoarthritis Radiographic and Pain Severity
,” Osteoarthritis Cartilage
, 19
(2
), pp. 186
–193
.61.
Chang
, A.
, Hurwitz
, D.
, Dunlop
, D.
, Song
, J.
, Cahue
, S.
, Hayes
, K.
, and Sharma
, L.
, 2007
, “The Relationship Between Toe-Out Angle During Gait and Progression of Medial Tibiofemoral Osteoarthritis
,” Ann. Rheumatol. Dis.
, 66
(10
), pp. 1271
–1275
.62.
Mündermann
, A.
, Dyrby
, C. O.
, and Andriacchi
, T. P.
, 2005
, “Secondary Gait Changes in Patients With Medial Compartment Knee Osteoarthritis: Increased Load at the Ankle, Knee, and Hip During Walking
,” Arthritis Rheumatol.
, 52
(9
), pp. 2835
–2844
.63.
Miller
, R. E.
, and Malfait
, A.-M.
, 2017
, “Osteoarthritis Pain: What are we Learning From Animal Models?
,” Best Pract. Res. Clin. Rheumatol.
, 31
(5
), pp. 676
–687
.64.
Malfait
, A. M.
, 2017
, “Why We Should Study Pain in Animal Models of Rheumatic Diseases
,” Clin. Exp. Rheumatol.
, 35
(5
), pp. S37
–S39
.https://www.ncbi.nlm.nih.gov/pubmed/2896736665.
Adebayo
, O. O.
, Ko
, F. C.
, Goldring
, S. R.
, Goldring
, M. B.
, Wright
, T. M.
, and van der Meulen
, M.
, 2017
, “Kinematics of Meniscal- and ACL-Transected Mouse Knees During Controlled Tibial Compressive Loading Captured Using Roentgen Stereophotogrammetry
,” J. Orthop. Res.
, 35
(2
), pp. 353
–360
.66.
Poulet
, B.
, Westerhof
, T. A. T.
, Hamilton
, R. W.
, Shefelbine
, S. J.
, and Pitsillides
, A. A.
, 2013
, “Spontaneous Osteoarthritis in Str/Ort Mice is Unlikely Due to Greater Vulnerability to Mechanical Trauma
,” Osteoarthritis Cartilage
, 21
(5
), pp. 756
–763
.67.
Sadeghi
, H.
, Espino
, D. M.
, and Shepherd
, D. E.
, 2015
, “Variation in Viscoelastic Properties of Bovine Articular Cartilage Below, Up to and Above Healthy Gait-Relevant Loading Frequencies
,” Proc. Inst. Mech. Eng. Part H
, 229
(2
), pp. 115
–123
.68.
Sadeghi
, H.
, Espino
, D. M.
, and Shepherd
, D. E. T.
, 2017
, “Fatigue Strength of Bovine Articular Cartilage-on-Bone Under Three-Point Bending: The Effect of Loading Frequency
,” BMC Musculoskeletal Disord.
, 18
(1
), p. 142
.69.
Kerin
, A. J.
, Wisnom
, M. R.
, and Adams
, M. A.
, 1998
, “The Compressive Strength of Articular Cartilage
,” Proc. Inst. Mech. Eng. Part H
, 212
(4
), pp. 273
–280
.70.
Adebayo
, O. O.
, Ko
, F. C.
, Wan
, P. T.
, Goldring
, S. R.
, Goldring
, M. B.
, Wright
, T. M.
, and van der Meulen
, M. C. H.
, 2017
, “Role of Subchondral Bone Properties and Changes in Development of Load-Induced Osteoarthritis in Mice
,” Osteoarthritis Cartilage
, 25
(12
), pp. 2108
–2118
.71.
Goldring
, M. B.
, and Marcu
, K. B.
, 2009
, “Cartilage Homeostasis in Health and Rheumatic Diseases
,” Arthritis Res. Ther.
, 11
(3
), p. 224
.72.
Ko
, F. C.
, Dragomir
, C. L.
, Plumb
, D. A.
, Hsia
, A. W.
, Adebayo
, O. O.
, Goldring
, S. R.
, Wright
, T. M.
, Goldring
, M. B.
, and van der Meulen
, M. C. H.
, 2016
, “Progressive Cell-Mediated Changes in Articular Cartilage and Bone in Mice Are Initiated by a Single Session of Controlled Cyclic Compressive Loading
,” J. Orthop. Res.
, 34
(11
), pp. 1941
–1949
.73.
Radin
, E. L.
, and Rose
, R. M.
, 1986
, “Role of Subchondral Bone in the Initiation and Progression of Cartilage Damage
,” Clin. Orthop. Relat. Res.
, 213
, pp. 34
–40
.https://www.ncbi.nlm.nih.gov/pubmed/378010474.
Burr
, D. B.
, and Utreja
, A.
, 2018
, “Editorial: Wnt Signaling Related to Subchondral Bone Density and Cartilage Degradation in Osteoarthritis
,” Arthritis Rheumatol.
, 70
(2
), pp. 157
–161
.75.
Holyoak
, D. T.
, Otero
, M.
, Armar
, N. A.
, Ziemian
, S. N.
, Otto
, A.
, Cullinane
, D.
, Wright
, T. M.
, Goldring
, S. R.
, Goldring
, M. B.
, and van der Meulen
, M. C. H.
, 2018
, “Collagen XI Mutation Lowers Susceptibility to Load-Induced Cartilage Damage in Mice
,” J. Orthop. Res.
, 36
(2
), pp. 711
–720
.76.
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 Rheumatol.
, 48
(9
), pp. 2509
–2518
.77.
Hu
, K.
, Xu
, L.
, Cao
, L.
, Flahiff
, C. M.
, Brussiau
, J.
, Ho
, K.
, Setton
, L. A.
, Youn
, I.
, Guilak
, F.
, Olsen
, B. R.
, and Li
, Y.
, 2006
, “Pathogenesis of Osteoarthritis-Like Changes in the Joints of Mice Deficient in Type IX Collagen
,” Arthritis Rheumatol.
, 54
(9
), pp. 2891
–2900
.78.
Buckland-Wright
, J. C.
, Messent
, E. A.
, Bingham
, C. O.
, Ward
, R. J.
, and Tonkin
, C.
, 2006
, “A 2 yr Longitudinal Radiographic Study Examining the Effect of a Bisphosphonate (Risedronate) Upon Subchondral Bone Loss in Osteoarthritic Knee Patients
,” Rheumatology
, 46
(2
), pp. 257
–264
.79.
Guo
, X.
, Day
, T. F.
, Jiang
, X.
, Garrett
, B. L.
, Topol
, L.
, and Yang
, Y.
, 2004
, “Wnt/Beta-Catenin Signaling is Sufficient and Necessary for Synovial Joint Formation
,” Genes Dev.
, 18
(19
), pp. 2404
–2417
.80.
Lane
, N. E.
, Nevitt
, M. C.
, Lui
, L.-Y.
, de Leon
, P.
, and Corr
, M.
, 2007
, “Wnt Signaling Antagonists are Potential Prognostic Biomarkers for the Progression of Radiographic Hip Osteoarthritis in Elderly Caucasian Women
,” Arthritis Rheumatol.
, 56
(10
), pp. 3319
–3325
.81.
Hopwood
, B.
, Tsykin
, A.
, Findlay
, D. M.
, and Fazzalari
, N. L.
, 2007
, “Microarray Gene Expression Profiling of Osteoarthritic Bone Suggests Altered Bone Remodelling, WNT and Transforming Growth Factor-Beta/Bone Morphogenic Protein Signalling
,” Arthritis Res. Ther.
, 9
(5
), p. R100
.82.
Power
, J.
, Poole
, K. E. S.
, van Bezooijen
, R.
, Doube
, M.
, Caballero-Alías
, A. M.
, Lowik
, C.
, Papapoulos
, S.
, Reeve
, J.
, and Loveridge
, N.
,. 2010
, “Sclerostin and the Regulation of Bone Formation: Effects in Hip Osteoarthritis and Femoral Neck Fracture
,” J. Bone Miner. Res.
, 25
(8
), pp. 1867
–1876
.83.
Kulkarni
, K.
, Karssiens
, T.
, Kumar
, V.
, and Pandit
, H.
, 2016
, “Obesity and Osteoarthritis
,” Maturitas
, 89
, pp. 22
–28
.84.
Enser
, M.
, 1972
, “Clearing-Factor Lipase in Obese Hyperglycaemic Mice (ob-ob)
,” Biochem. J.
, 129
(2
), pp. 447
–453
.85.
Surwit
, R. S.
, Kuhn
, C. M.
, Cochrane
, C.
, McCubbin
, J. A.
, and Feinglos
, M. N.
, 1988
, “Diet-Induced Type II Diabetes in C57BL/6J Mice
,” Diabetes
, 37
(9
), pp. 1163
–1167
.86.
Guss
, J. D.
, Ziemian
, S. N.
, Luna
, M.
, Sandoval
, T. N.
, Holyoak
, D. T.
, Guisado
, G. G.
, Roubert
, S.
, Callahan
, R. L.
, Brito
, I. L.
, van der Meulen
, M. C. H.
, Goldring
, S. R.
, and Hernandez
, C. J.
, 2019
, “The Effects of Metabolic Syndrome, Obesity, and the Gut Microbiome on Load-Induced Osteoarthritis
,” Osteoarthritis Cartilage
, 27
(1
), pp. 129
–139
.87.
Duan
, X.
, Sandell
, L. J.
, Chinzei
, N.
, Holguin
, N.
, Silva
, M. J.
, Schiavinato
, A.
, and Rai
, M. F.
, 2017
, “Therapeutic Efficacy of Intra-Articular Hyaluronan Derivative and Platelet-Rich Plasma in Mice Following Axial Tibial Loading
,” PLoS One
, 12
(4
), p. e0175682
.88.
Altman
, R.
, Lim
, S.
, Steen
, R. G.
, and Dasa
, V.
, 2015
, “Hyaluronic Acid Injections Are Associated With Delay of Total Knee Replacement Surgery in Patients With Knee Osteoarthritis: Evidence From a Large U.S. Health Claims Database
,” PLoS One
, 10
(12
), p. e0145776
.89.
Hayami
, T.
, Pickarski
, M.
, Wesolowski
, G. A.
, McLane
, J.
, Bone
, A.
, Destefano
, J.
, Rodan
, G. A.
, and Duong
, L. T.
,. 2004
, “The Role of Subchondral Bone Remodeling in Osteoarthritis: Reduction of Cartilage Degeneration and Prevention of Osteophyte Formation by Alendronate in the Rat Anterior Cruciate Ligament Transection Model
,” Arthritis Rheumatol.
, 50
(4
), pp. 1193
–1206
.90.
Kang
, M. L.
, and Im
, I.
, 2014
, “Drug Delivery Systems for Intra-Articular Treatment of Osteoarthritis
,” Expert Opin. Drug Deliv.
, 11
(2
), pp. 269
–282
.91.
Whitmire
, R. E.
, Scott Wilson
, D.
, Singh
, A.
, Levenston
, M. E.
, Murthy
, N.
, and García
, A. J.
, 2012
, “Self-Assembling Nanoparticles for Intra-Articular Delivery of Anti-Inflammatory Proteins
,” Biomaterials
, 33
(30
), pp. 7665
–7675
.92.
Singh
, A.
, Agarwal
, R.
, Diaz-Ruiz
, C. A.
, Willett
, N. J.
, Wang
, P.
, Lee
, L. A.
, Wang
, Q.
, Guldberg
, R. E.
, and García
, A. J.
, 2014
, “Nanoengineered Particles for Enhanced Intra-Articular Retention and Delivery of Proteins
,” Adv. Healthcare Mater.
, 3
(10
), pp. 1562
–1567
.93.
He
, Z.
, Wang
, B.
, Hu
, C.
, and Zhao
, J.
, 2017
, “An Overview of Hydrogel-Based Intra-Articular Drug Delivery for the Treatment of Osteoarthritis
,” Colloids Surf. B Biointerfaces
, 154
, pp. 33
–39
.94.
Seliktar
, D.
, 2012
, “Designing Cell-Compatible Hydrogels for Biomedical Applications
,” Science
, 336
(6085
), pp. 1124
–1128
.95.
Krishnan
, Y.
, Rees
, H. A.
, Rossitto
, C. P.
, Kim
, S.-E.
, Hung
, H.-H. K.
, Frank
, E. H.
, Olsen
, B. D.
, Liu
, D. R.
, Hammond
, P. T.
, and Grodzinsky
, A. J.
,. 2018
, “Green Fluorescent Proteins Engineered for Cartilage-Targeted Drug Delivery: Insights for Transport Into Highly Charged Avascular Tissues
,” Biomaterials
, 183
, pp. 218
–233
.96.
Phillips
, E. R.
, Prudnikova
, K.
, Bui
, T.
, Taylor
, A. J.
, Galindo
, D. A.
, Huneke
, R. B.
, Hou
, J. S.
, Mulcahey
, M. K.
, and Marcolongo
, M. S.
, 2019
, “Biomimetic Proteoglycans Can Molecularly Engineer Early Osteoarthritic Cartilage In Vivo
,” J. Orthop. Res.
, 37
(2
), pp. 403
–411
.97.
Hamamura
, K.
, Zhang
, P.
, Zhao
, L.
, Shim
, J. W.
, Chen
, A.
, Dodge
, T. R.
, Wan
, Q.
, Shih
, H.
, Na
, S.
, Lin
, C. C.
, Sun
, H. B.
, and Yokota
, H.
, 2013
, “Knee Loading Reduces MMP13 Activity in the Mouse Cartilage
,” BMC Musculoskeletal Disord.
, 14
(1
), p. 312
.98.
Nomura
, M.
, Sakitani
, N.
, Iwasawa
, H.
, Kohara
, Y.
, Takano
, S.
, Wakimoto
, Y.
, Kuroki
, H.
, and Moriyama
, H.
, 2017
, “Thinning of Articular Cartilage After Joint Unloading or Immobilization. An Experimental Investigation of the Pathogenesis in Mice
,” Osteoarthritis Cartilage
, 25
(5
), pp. 727
–736
.99.
Mistry
, D. A.
, Chandratreya
, A.
, and Lee
, P. Y. F.
, 2018
, “An Update on Unloading Knee Braces in the Treatment of Unicompartmental Knee Osteoarthritis From the Last 10 Years: A Literature Review
,” Surg. J.
, 4
(3), pp. 110
–118
.100.
Abusara
, Z.
, Von Kossel
, M.
, and Herzog
, W.
, 2016
, “In Vivo Dynamic Deformation of Articular Cartilage in Intact Joints Loaded by Controlled Muscular Contractions
,” PLoS One
, 11
(1
), p. e0147547
.101.
Correia
, C.
, Pereira
, A. L.
, Duarte
, A. R. C.
, Frias
, A. M.
, Pedro
, A. J.
, Oliveira
, J. T.
, Sousa
, R. A.
, and Reis
, R. L.
, 2012
, “Dynamic Culturing of Cartilage Tissue: The Significance of Hydrostatic Pressure
,” Tissue Eng.
, 18
(19–20
), pp. 1979
–1991
.Copyright © 2019 by ASME
You do not currently have access to this content.
