title: Intermittent applied mechanical loading induces subchondral bone thickening that may be intensified locally by contiguous articular cartilage lesions.
abstract: OBJECTIVE
  Changes in subchondral bone (SCB) and cross-talk with articular cartilage (AC) have been linked to osteoarthritis (OA). Using micro-computed tomography (micro-CT) this study: (1) examines changes in SCB architecture in a non-invasive loading mouse model in which focal AC lesions are induced selectively in the lateral femur, and (2) determines any modifications in the contralateral knee, linked to changes in gait, which might complicate use of this limb as an internal control.
  
  
  METHODS
  Right knee joints of CBA mice were loaded: once with 2 weeks of habitual use (n = 7), for 2 weeks (n = 8) or for 5 weeks (n = 5). Both left (contralateral) and right (loaded) knees were micro-CT scanned and the SCB and trabecular bone analysed. Gait analysis was also performed.
  
  
  RESULTS
  These analyses showed a significant increase in SCB thickness in the lateral compartments in joints loaded for 5 weeks, which was most marked in the lateral femur; the contralateral non-loaded knee also showed transient SCB thickening (loaded once and repetitively). Epiphyseal trabecular bone BV/TV and trabecular thickness were also increased in the lateral compartments after 5 weeks of loading, and in all joint compartments in the contralateral knee. Gait analysis showed that applied loading only affected gait in the contralateral himd-limb in all groups of mice from the second week after the first loading episode.
  
  
  CONCLUSIONS
  These data indicate a spatial link between SCB thickening and AC lesions following mechanical trauma, and the clear limitations associated with the use of contralateral joints as controls in such OA models, and perhaps in OA diagnosis.
authors: University College London, Royal Free Campus, London, UK.
authors: B
authors: B
authors: Poulet
authors: Universidade Federal do Mato Grosso, Mato Grosso, Brazil.
authors: R
authors: R
authors: de Souza
authors: Royal Veterinary College, London, UK.
authors: A V
authors: AV
authors: Kent
authors: Royal Veterinary College, London, UK.
authors: L
authors: L
authors: Saxon
authors: Royal Veterinary College, London, UK.
authors: O
authors: O
authors: Barker
authors: Royal Veterinary College, London, UK.
authors: A
authors: A
authors: Wilson
authors: Royal Veterinary College, London, UK.
authors: Y-M
authors: YM
authors: Chang
authors: Murdoch University, Perth, Australia.
authors: M
authors: M
authors: Cake
authors: Royal Veterinary College, London, UK. Electronic address: apitsillides@rvc.ac.uk.
authors: A A
authors: AA
authors: Pitsillides
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D002358:Cartilage, Articular / Q000293:injuries*; D004838:Epiphyses / Q000473:pathology; D005269:Femur / Q000473:pathology* / Q000503:physiopathology; D005684:Gait / Q000502:physiology; D008297:Male; D008808:Mice, Inbred CBA; D009043:Motor Activity / Q000502:physiology; D010003:Osteoarthritis / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D013314:Stress, Mechanical; D013977:Tibia / Q000473:pathology* / Q000503:physiopathology; D016474:Weight-Bearing / Q000502:physiology; D055114:X-Ray Microtomography
keywords: Articular cartilage; Joint; Mechanical loading; Subchondral bone and osteoarthritis
references: Arthritis Rheumatol. 2014 Jul;66(7):1832-42
references: 24623711
references: Osteoarthritis Cartilage. 2013 May;21(5):756-63
references: 23467034
references: Osteoarthritis Cartilage. 2000 Jul;8(4):248-57
references: 10903878
references: Am J Vet Res. 2001 Aug;62(8):1207-11
references: 11497439
references: Calcif Tissue Int. 2002 Apr;70(4):320-9
references: 12004337
references: Osteoarthritis Cartilage. 2003 Jun;11(6):412-23
references: 12801481
references: Curr Opin Rheumatol. 2003 Sep;15(5):628-33
references: 12960492
references: Arthritis Rheum. 2004 Feb;50(2):341-4
references: 14872473
references: J Rheumatol Suppl. 2004 Apr;70:77-80
references: 15132360
references: Arthritis Rheum. 2004 Aug;50(8):2547-58
references: 15334469
references: Int J Biochem Cell Biol. 2005 Jan;37(1):224-36
references: 15381164
references: Acta Orthop Scand. 1979 Oct;50(5):501-6
references: 525314
references: Clin Orthop Relat Res. 1986 Dec;(213):34-40
references: 3780104
references: Calcif Tissue Int. 1991 Jul;49(1):20-6
references: 1893292
references: Microsc Res Tech. 1997 May 15;37(4):343-57
references: 9185156
references: Physiol Behav. 1997 Nov;62(5):951-4
references: 9333186
references: J Endocrinol. 1997 Dec;155(3):411-21
references: 9487986
references: J Rheumatol. 2005 Feb;32(2):325-34
references: 15693095
references: Osteoarthritis Cartilage. 2005 Nov;13(11):979-87
references: 16243232
references: Bone. 2005 Dec;37(6):810-8
references: 16198164
references: Biorheology. 2006;43(3-4):379-88
references: 16912410
references: J Orthop Res. 2007 May;25(5):578-92
references: 17266145
references: BMC Vet Res. 2007;3:16
references: 17683523
references: Arthritis Res Ther. 2007;9(6):R123
references: 18036238
references: Best Pract Res Clin Rheumatol. 2008 Aug;22(4):657-75
references: 18783743
references: Osteoarthritis Cartilage. 2009 May;17(5):636-45
references: 19010693
references: Bone. 2009 Sep;45(3):414-22
references: 19481620
references: Pharmacol Biochem Behav. 2011 Jan;97(3):603-10
references: 21111752
references: Arthritis Rheum. 2011 Jan;63(1):137-47
references: 20882669
references: Arthritis Res Ther. 2011;13(2):R46
references: 21418601
references: Arthritis Rheum. 2011 Dec;63(12):3853-8
references: 22127702
references: Bone. 2012 Aug;51(2):212-7
references: 22197997
references: Osteoarthritis Cartilage. 2012 Jul;20(7):773-82
references: 22531459
references: Arthritis Rheum. 2013 Jun;65(6):1569-78
references: 23436303
references: Curr Osteoporos Rep. 2014 Mar;12(1):127-34
references: 24458429