title: The mechanobiological aetiopathogenesis of tendinopathy: is it the over-stimulation or the under-stimulation of tendon cells?
abstract: While there is a significant amount of information available on the clinical presentation(s) and pathological changes associated with tendinopathy, the precise aetiopathogenesis of this condition remains a topic of debate. Classically, the aetiology of tendinopathy has been linked to the performance of repetitive activities (so-called overuse injuries). This has led many investigators to suggest that it is the mechanobiologic over-stimulation of tendon cells that is the initial stimulus for the degradative processes which have been shown to accompany tendinopathy. Although several studies have been able to demonstrate that the in vitro over-stimulation of tendon cells in monolayer can result in a pattern(s) of gene expression seen in clinical cases of tendinopathy, the strain magnitudes and durations used in these in vitro studies, as well as the model systems, may not be clinically relevant. Using a rat tail tendon model, we have studied the in vitro mechanobiologic response of tendon cells in situ to various tensile loading regimes. These studies have led to the hypothesis that the aetiopathogenic stimulus for the degenerative cascade which precedes the overt pathologic development of tendinopathy is the catabolic response of tendon cells to mechanobiologic under-stimulation as a result of microscopic damage to the collagen fibres of the tendon. In this review, we examine the rationale for this hypothesis and provide evidence in support of this theory.
authors: Laboratory for Comparative Orthopaedic Research, Veterinary Medical Center, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA. arnoczky@cvm.msu.edu
authors: Steven P
authors: SP
authors: Arnoczky
authors: Michael
authors: M
authors: Lavagnino
authors: Monika
authors: M
authors: Egerbacher
mesh_terms: D000818:Animals; D012090:Cumulative Trauma Disorders / Q000150:complications; D020782:Matrix Metalloproteinases / Q000502:physiology; D018613:Microscopy, Confocal; D051381:Rats; D013314:Stress, Mechanical; D052256:Tendinopathy / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology
chemical_list: D020782:Matrix Metalloproteinases
references: Matrix Biol. 2001 Jun;20(3):159-69
references: 11420148
references: Connect Tissue Res. 1978;6(1):11-23
references: 149646
references: J Biomech. 1980;13(10):887-93
references: 7462263
references: Biorheology. 1982;19(3):385-96
references: 7104480
references: Arch Orthop Trauma Surg. 1986;105(2):113-20
references: 3718188
references: Crit Rev Biomed Eng. 1988;16(2):141-69
references: 2460290
references: Arch Orthop Trauma Surg. 1990;110(1):15-21
references: 2288799
references: FASEB J. 1991 Apr;5(7):2013-9
references: 1707019
references: Bioessays. 1991 May;13(5):207-12
references: 1654048
references: Curr Opin Cell Biol. 1991 Oct;3(5):841-8
references: 1931084
references: J Bone Joint Surg Am. 1991 Dec;73(10):1507-25
references: 1748700
references: J Cell Biol. 1992 Apr;117(1):83-93
references: 1556158
references: Med Sci Sports Exerc. 1993 May;25(5):603-7
references: 8388071
references: Science. 1993 May 21;260(5111):1124-7
references: 7684161
references: Biophys J. 1994 Jun;66(6):2181-9
references: 8075352
references: Biochim Biophys Acta. 1995 Jul 28;1242(1):77-98
references: 7542926
references: Sports Med. 1995 Aug;20(2):77-89
references: 7481284
references: J Orthop Res. 1995 Nov;13(6):907-14
references: 8544028
references: J Orthop Res. 1996 Mar;14(2):216-22
references: 8648498
references: J Biomech. 1995 Dec;28(12):1505-13
references: 8666590
references: Biochem Cell Biol. 1995 Jul-Aug;73(7-8):349-65
references: 8703408
references: J Orthop Res. 1996 Sep;14(5):729-35
references: 8893765
references: Annu Rev Physiol. 1997;59:575-99
references: 9074778
references: Science. 1997 May 30;276(5317):1345-6
references: 9190676
references: Scand J Med Sci Sports. 1997 Apr;7(2):86-95
references: 9211609
references: J Cell Physiol. 1998 Jun;175(3):323-32
references: 9572477
references: Physiol Rev. 1998 Jul;78(3):763-81
references: 9674694
references: Exp Cell Res. 1999 May 1;248(2):608-19
references: 10222153
references: Osteoarthritis Cartilage. 1999 Jan;7(1):141-53
references: 10367022
references: J Biomech. 2005 Jan;38(1):69-75
references: 15519341
references: Connect Tissue Res. 2001;42(1):13-23
references: 11696985
references: Med Sci Sports Exerc. 2001 Dec;33(12):1983-90
references: 11740288
references: Matrix Biol. 2002 Mar;21(2):185-95
references: 11852234
references: J Orthop Res. 2002 Jan;20(1):29-35
references: 11853087
references: J Orthop Res. 2002 Jan;20(1):36-9
references: 11853088
references: Eur J Histochem. 2002;46(1):3-12
references: 12044045
references: J Orthop Res. 2002 Sep;20(5):947-52
references: 12382958
references: J Orthop Res. 2002 Nov;20(6):1372-9
references: 12472255
references: Comp Biochem Physiol A Mol Integr Physiol. 2002 Dec;133(4):987-1000
references: 12485688
references: J Comp Pathol. 2005 Jan;132(1):51-8
references: 15629479
references: J Bone Joint Surg Am. 2005 Jan;87(1):187-202
references: 15634833
references: Br J Sports Med. 2005 May;39(5):e25
references: 15849278
references: J Orthop Res. 2005 Sep;23(5):1211-8
references: 15908162
references: J Shoulder Elbow Surg. 2005 Sep-Oct;14(5):535-41
references: 16194748
references: Br J Sports Med. 2005 Nov;39(11):789-91
references: 16244185
references: Clin Orthop Relat Res. 2006 Feb;443:320-32
references: 16462458
references: Arthritis Rheum. 2006 Mar;54(3):832-42
references: 16508964
references: J Biomech. 2006;39(9):1563-82
references: 16000201
references: J Biomech. 2006;39(13):2355-62
references: 16256123
references: Acta Orthop Scand. 2002 Dec;73(6):658-62
references: 12553513
references: J Cell Biochem. 2003 Jun 1;89(3):556-62
references: 12761889
references: Structure. 2003 Sep;11(9):1179-88
references: 12962636
references: Connect Tissue Res. 2003;44(3-4):128-33
references: 14504032
references: Connect Tissue Res. 2003;44(3-4):181-7
references: 14504039
references: J Orthop Res. 2003 Nov;21(6):970-5
references: 14554207
references: Clin Sports Med. 2003 Oct;22(4):693-701
references: 14560541
references: Rheumatology (Oxford). 2004 Feb;43(2):131-42
references: 12867575
references: J Orthop Res. 2004 Mar;22(2):328-33
references: 15013092
references: Am J Sports Med. 2004 Jul-Aug;32(5):1223-9
references: 15262646
references: Z Anat Entwicklungsgesch. 1968;127(2):154-64
references: 5678653
references: Knee Surg Sports Traumatol Arthrosc. 2001 Sep;9(5):322-6
references: 11685366