title: Dynamic and static overloading induce early degenerative processes in caprine lumbar intervertebral discs.
abstract: Mechanical overloading of the spine is associated with low back pain and intervertebral disc (IVD) degeneration. How excessive loading elicits degenerative changes in the IVD is poorly understood. Comprehensive knowledge of the interaction between mechanical loading, cell responses and changes in the extracellular matrix of the disc is needed in order to successfully intervene in this process. The purpose of the current study was to investigate whether dynamic and static overloading affect caprine lumbar discs differently and what mechanisms lead to mechanically induced IVD degeneration. Lumbar caprine IVDs (n = 175) were cultured 7, 14 and 21 days under simulated-physiological loading (control), high dynamic or high static loading. Axial deformation and stiffness were continuously measured. Cell viability, cell density, and gene expression were assessed in the nucleus, inner- and outer annulus. The extracellular matrix (ECM) was analyzed for water, glycosaminoglycan and collagen content. IVD height loss and changes in axial deformation were gradual with dynamic and acute with static overloading. Dynamic overloading caused cell death in all IVD regions, whereas static overloading mostly affected the outer annulus. IVDs expression of catabolic and inflammation-related genes was up-regulated directly, whereas loss of water and glycosaminoglycan were significant only after 21 days. Static and dynamic overloading both induced pathological changes to caprine lumbar IVDs within 21 days. The mechanism by which they inflict biomechanical, cellular, and extracellular changes to the nucleus and annulus differed. The described cascades provide leads for the development of new pharmacological and rehabilitative therapies to halt the progression of DDD.
authors: Department of Orthopaedic Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors: Cornelis P L
authors: CP
authors: Paul
authors: Tom
authors: T
authors: Schoorl
authors: Hendrik A
authors: HA
authors: Zuiderbaan
authors: Behrouz
authors: B
authors: Zandieh Doulabi
authors: Albert J
authors: AJ
authors: van der Veen
authors: Peter M
authors: PM
authors: van de Ven
authors: Theo H
authors: TH
authors: Smit
authors: Barend J
authors: BJ
authors: van Royen
authors: Marco N
authors: MN
authors: Helder
authors: Margriet G
authors: MG
authors: Mullender
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D005109:Extracellular Matrix / Q000378:metabolism; D005786:Gene Expression Regulation; D006041:Goats; D007403:Intervertebral Disc / Q000378:metabolism / Q000473:pathology*; D055959:Intervertebral Disc Degeneration / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008161:Lumbosacral Region / Q000473:pathology*; D016474:Weight-Bearing
references: Biomaterials. 2006 Jan;27(3):377-87
references: 16168476
references: Spine (Phila Pa 1976). 2010 Sep 1;35(19):1744-52
references: 20395884
references: Spine (Phila Pa 1976). 2008 Apr 20;33(9):949-54
references: 18427314
references: J Pathol. 2008 Mar;214(4):523-30
references: 18200629
references: Spine (Phila Pa 1976). 2004 Dec 1;29(23):2700-9
references: 15564919
references: Eur Spine J. 2011 Nov;20(11):1796-812
references: 21541667
references: J Biomech. 2007;40(10):2230-5
references: 17182043
references: Biochem Cell Biol. 2010 Jun;88(3):539-52
references: 20555395
references: Eur Cell Mater. 2008 Feb 05;15:11-26
references: 18247274
references: J Orthop Res. 2009 Sep;27(9):1235-42
references: 19274755
references: Spine J. 2010 Nov;10(11):958-60
references: 20970736
references: J Biomech. 2010 Apr 19;43(6):1067-73
references: 20116063
references: Arthritis Res Ther. 2009;11(6):R166
references: 19889209
references: Spine (Phila Pa 1976). 2006 Aug 15;31(18):2151-61
references: 16915105
references: PLoS One. 2012;7(3):e33147
references: 22427972
references: Arthritis Rheum. 2008 Jun;58(6):1664-73
references: 18512787
references: Matrix Biol. 2010 Apr;29(3):209-18
references: 20005293
references: J Orthop Res. 1999 Sep;17(5):732-7
references: 10569484
references: Med Eng Phys. 2004 Sep;26(7):587-94
references: 15271286
references: Biochem Soc Trans. 2002 Nov;30(Pt 6):853-8
references: 12440932
references: Spine (Phila Pa 1976). 2008 Feb 15;33(4):356-65
references: 18277865
references: Matrix Biol. 2004 Jan;22(7):573-83
references: 14996437
references: Biotechniques. 1997 Apr;22(4):656-8
references: 9105617
references: Spine (Phila Pa 1976). 1996 May 15;21(10):1174-84
references: 8727192
references: Spine (Phila Pa 1976). 2010 Oct 1;35(21):1925-9
references: 20838276
references: Spine J. 2011 Jan;11(1):36-43
references: 21056011
references: Spine (Phila Pa 1976). 2008 Jul 15;33(16):1714-21
references: 18628703
references: J Orthop Res. 2012 Jan;30(1):112-21
references: 21674606
references: J Orthop Res. 2004 Nov;22(6):1193-200
references: 15475197
references: Biorheology. 1984;21(5):675-86
references: 6518283
references: Spine J. 2009 Jan-Feb;9(1):47-59
references: 19111259
references: Eur Spine J. 2002 Apr;11(2):137-44
references: 11956920
references: Spine (Phila Pa 1976). 2009 Apr 20;34(9):934-40
references: 19532001
references: Spine (Phila Pa 1976). 2005 Sep 1;30(17):1940-8
references: 16135983
references: J Bone Joint Surg Am. 2006 Apr;88 Suppl 2:30-5
references: 16595440
references: Methods Mol Biol. 2010;622:312-47
references: 20135291
references: Eur J Vasc Endovasc Surg. 2009 Jun;37(6):661-70
references: 19328027
references: J Clin Invest. 1996 Aug 15;98(4):996-1003
references: 8770872
references: Spine (Phila Pa 1976). 2004 Dec 1;29(23):2724-32
references: 15564921
references: J Neurosurg. 1995 Jun;82(6):1095
references: 7760187
references: Spine (Phila Pa 1976). 1999 Apr 15;24(8):755-62
references: 10222525
references: Arthritis Res Ther. 2011 Jan 28;13(1):R8
references: 21276216
references: Eur Spine J. 2006 Aug;15 Suppl 3:S372-8
references: 16680448
references: J Biomech. 2004 Aug;37(8):1165-75
references: 15212921
references: Arthritis Rheum. 2010 Nov;62(11):3385-94
references: 20617521
references: Spine (Phila Pa 1976). 2007 Nov 1;32(23):2521-8
references: 17978649
references: J Biomech. 2004 Mar;37(3):329-37
references: 14757452
references: J Biomech. 2008;41(6):1260-8
references: 18328489
references: Spine (Phila Pa 1976). 2008 Jun 1;33(13):1403-9
references: 18520935
references: Spine (Phila Pa 1976). 2011 Apr 15;36(8):593-9
references: 21178846
references: Spine (Phila Pa 1976). 2008 Dec 1;33(25):2767-73
references: 19050583
references: Eur Spine J. 2008 Jan;17(1):2-19
references: 17632738
references: Osteoarthritis Cartilage. 2011 Aug;19(8):1011-8
references: 21549847
references: J Bone Joint Surg Am. 2006 Apr;88 Suppl 2:52-7
references: 16595444
references: Matrix Biol. 2006 Sep;25(7):409-18
references: 16934445
references: Nature. 2005 Mar 31;434(7033):644-8
references: 15800624
references: Med Eng Phys. 2009 Jul;31(6):642-9
references: 19196536