title: Comparison of loading rate-dependent injury modes in a murine model of post-traumatic osteoarthritis.
abstract: Post-traumatic osteoarthritis (PTOA) is a common long-term consequence of joint injuries such as anterior cruciate ligament (ACL) rupture. In this study we used a tibial compression overload mouse model to compare knee injury induced at low speed (1 mm/s), which creates an avulsion fracture, to injury induced at high speed (500 mm/s), which induces midsubstance tear of the ACL. Mice were sacrificed at 0 days, 10 days, 12 weeks, or 16 weeks post-injury, and joints were analyzed with micro-computed tomography, whole joint histology, and biomechanical laxity testing. Knee injury with both injury modes caused considerable trabecular bone loss by 10 days post-injury, with the Low Speed Injury group (avulsion) exhibiting a greater amount of bone loss than the High Speed Injury group (midsubstance tear). Immediately after injury, both injury modes resulted in greater than twofold increases in total AP joint laxity relative to control knees. By 12 and 16 weeks post-injury, total AP laxity was restored to uninjured control values, possibly due to knee stabilization via osteophyte formation. This model presents an opportunity to explore fundamental questions regarding the role of bone turnover in PTOA, and the findings of this study support a biomechanical mechanism of osteophyte formation following injury.
authors.affiliation: Department of Orthopaedic Surgery, University of California-Davis Medical Center, 4635 2nd Ave, Suite 2000, Sacramento, California, 95817.
authors.forename: Kevin A
authors.initials: KA
authors.lastname: Lockwood
authors.forename: Bryce T
authors.initials: BT
authors.lastname: Chu
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Anderson
authors.forename: Dominik R
authors.initials: DR
authors.lastname: Haudenschild
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Christiansen
mesh_terms: D000818:Animals; D016118:Anterior Cruciate Ligament / Q000000981:diagnostic imaging / Q000503:physiopathology*; D000070598:Anterior Cruciate Ligament Injuries; D001696:Biomechanical Phenomena / Q000502:physiology; D004195:Disease Models, Animal; D005269:Femur / Q000000981:diagnostic imaging / Q000502:physiology; D007593:Joint Instability / Q000000981:diagnostic imaging / Q000503:physiopathology*; D007718:Knee Injuries / Q000000981:diagnostic imaging / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000503:physiopathology*; D054850:Osteophyte / Q000000981:diagnostic imaging / Q000503:physiopathology; D013977:Tibia / Q000000981:diagnostic imaging / Q000502:physiology; D016474:Weight-Bearing / Q000502:physiology; D055114:X-Ray Microtomography
keywords: ACL injury; joint stability; mouse model; osteophyte; post-traumatic osteoarthritis
references.citation: Epidemiol Rev. 1988;10:1-28
references.pmid: 3066625
references.citation: Bone. 2006 Feb;38(2):234-43
references.pmid: 16185945
references.citation: Radiology. 2008 Sep;248(3):737-47
references.pmid: 18710973
references.citation: Int Orthop. 2005 Dec;29(6):375-9
references.pmid: 16167157
references.citation: Arthritis Rheum. 2011 Sep;63(9):2561-3
references.pmid: 21360518
references.citation: J Trauma. 1976 Feb;16(2):99-105
references.pmid: 1255835
references.citation: Osteoarthritis Cartilage. 2011 Feb;19(2):163-70
references.pmid: 21094262
references.citation: J Orthop Res. 2007 May;25(5):578-92
references.pmid: 17266145
references.citation: Am J Sports Med. 2009 Jul;37(7):1434-43
references.pmid: 19567666
references.citation: Osteoarthritis Cartilage. 2010 Oct;18 Suppl 3:S17-23
references.pmid: 20864019
references.citation: Am J Sports Med. 2007 Oct;35(10):1756-69
references.pmid: 17761605
references.citation: Osteoarthritis Cartilage. 2000 Jan;8(1):25-33
references.pmid: 10607496
references.citation: J Biomech. 1996 Jun;29(6):799-806
references.pmid: 9147978
references.citation: J Orthop Res. 2006 Jun;24(6):1200-7
references.pmid: 16705702
references.citation: Osteoarthritis Cartilage. 2008 Oct;16(10):1150-9
references.pmid: 18387828
references.citation: Br J Rheumatol. 1997 Jan;36(1):16-9
references.pmid: 9117167
references.citation: J Bone Joint Surg Am. 1974 Mar;56(2):236-53
references.pmid: 4452684
references.citation: Clin Orthop Relat Res. 1986 Dec;(213):34-40
references.pmid: 3780104
references.citation: J Bone Miner Res. 2010 Jul;25(7):1468-86
references.pmid: 20533309
references.citation: Radiographics. 2008 Oct;28(6):1755-70
references.pmid: 18936034
references.citation: Osteoarthritis Cartilage. 2012 Jul;20(7):773-82
references.pmid: 22531459
references.citation: Osteoporos Int. 2012 Feb;23(2):589-97
references.pmid: 21359670
references.citation: Osteoarthritis Cartilage. 2007 Sep;15(9):1061-9
references.pmid: 17470400
references.citation: Arthritis Rheum. 1990 Jun;33(6):853-8
references.pmid: 2363739
references.citation: Arthritis Rheum. 2011 Jan;63(1):137-47
references.pmid: 20882669