BMC Musculoskeletal Disorders | |
Stochastic amplitude-modulated stretching of rabbit flexor digitorum profundus tendons reduces stiffness compared to cyclic loading but does not affect tenocyte metabolism | |
Benjamin Gantenbein-Ritter1  Stephen J Ferguson2  Alexander Bürki1  Thomas H Steiner2  | |
[1] Institute for Surgical Technology and Biomechanics, University of Bern, Stauffacherstrasse 78, Bern, CH-3014, Switzerland;Institute for Biomechanics, ETH Zürich, Zürich, Switzerland | |
关键词: Cell activity; Gene expression; Proteoglycan production; Strain control; Stochastic amplitude-modulation; Tensile stiffness; Tendon; | |
Others : 1135729 DOI : 10.1186/1471-2474-13-222 |
|
received in 2012-02-13, accepted in 2012-11-08, 发布年份 2012 | |
【 摘 要 】
Background
It has been demonstrated that frequency modulation of loading influences cellular response and metabolism in 3D tissues such as cartilage, bone and intervertebral disc. However, the mechano-sensitivity of cells in linear tissues such as tendons or ligaments might be more sensitive to changes in strain amplitude than frequency. Here, we hypothesized that tenocytes in situ are mechano-responsive to random amplitude modulation of strain.
Methods
We compared stochastic amplitude-modulated versus sinusoidal cyclic stretching. Rabbit tendon were kept in tissue-culture medium for twelve days and were loaded for 1h/day for six of the total twelve culture days. The tendons were randomly subjected to one of three different loading regimes: i) stochastic (2 – 7% random strain amplitudes), ii) cyclic_RMS (2–4.42% strain) and iii) cyclic_high (2 - 7% strain), all at 1 Hz and for 3,600 cycles, and one unloaded control.
Results
At the end of the culture period, the stiffness of the “stochastic” group was significantly lower than that of the cyclic_RMS and cyclic_high groups (both, p < 0.0001). Gene expression of eleven anabolic, catabolic and inflammatory genes revealed no significant differences between the loading groups.
Conclusions
We conclude that, despite an equivalent metabolic response, stochastically stretched tendons suffer most likely from increased mechanical microdamage, relative to cyclically loaded ones, which is relevant for tendon regeneration therapies in clinical practice.
【 授权许可】
2012 Steiner et al.; licensee BioMed Central Ltd.
【 预 览 】
Files | Size | Format | View |
---|---|---|---|
20150311050447812.pdf | 1989KB | download | |
Figure 6. | 33KB | Image | download |
Figure 5. | 54KB | Image | download |
Figure 4. | 33KB | Image | download |
Figure 3. | 69KB | Image | download |
Figure 6. | 67KB | Image | download |
Figure 1. | 41KB | Image | download |
【 图 表 】
Figure 1.
Figure 6.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
【 参考文献 】
- [1]Wilson JJ, Best TM: Common overuse tendon problems: A review and recommendations for treatment. Am Fam Physician 2005, 72(5):811-818.
- [2]Asundi KR, Kursa K, Lotz J, Rempel DM: In vitro system for applying cyclic loads to connective tissues under displacement or force control. Ann Biomed Eng 2007, 35(7):1188-1195.
- [3]Sharma P, Maffulli N: Biology of tendon injury: healing, modeling and remodeling. J Musculoskelet Neuronal Interact 2006, 6(2):181-190.
- [4]Wang JH: Mechanobiology of tendon. J Biomech 2006, 39(9):1563-1582.
- [5]Nakama LH, King KB, Abrahamsson S, Rempel DM: Evidence of tendon microtears due to cyclical loading in an in vivo tendinopathy model. J Orthop Res 2005, 23(5):1199-1205.
- [6]Lavagnino M, Arnoczky SP, Tian T, Vaupel Z: Effect of amplitude and frequency of cyclic tensile strain on the inhibition of MMP-1 mRNA expression in tendon cells: an in vitro study. Connect Tissue Res 2003, 44(3–4):181-187.
- [7]Lavagnino M, Arnoczky SP, Kepich E, Caballero O, Haut RC: A finite element model predicts the mechanotransduction response of tendon cells to cyclic tensile loading. Biomech Model Mechanobiol 2008, 7(5):405-416.
- [8]Gardner K, Arnoczky SP, Lavagnino M: Effect of in vitro stress-deprivation and cyclic loading on the length of tendon cell cilia in situ. J Orthop Res 2011, 29(4):582-587.
- [9]Hannafin JA, Arnoczky SP, Hoonjan A, Torzilli PA: Effect of stress deprivation and cyclic tensile loading on the material and morphologic properties of canine flexor digitorum profundus tendon: an in vitro study. J Orthop Res 1995, 13(6):907-914.
- [10]Thornton GM, Shao X, Chung M, Sciore P, Boorman RS, Hart DA, Lo IK: Changes in mechanical loading lead to tendonspecific alterations in MMP and TIMP expression: influence of stress deprivation and intermittent cyclic hydrostatic compression on rat supraspinatus and Achilles tendons. Br J Sports Med 2010, 44(10):698-703.
- [11]Arnoczky SP, Tian T, Lavagnino M, Gardner K: Ex vivo static tensile loading inhibits MMP-1 expression in rat tail tendon cells through a cytoskeletally based mechanotransduction mechanism. J Orthop Res 2004, 22(2):328-333.
- [12]Qi J, Chi L, Bynum D, Banes AJ: Gap junctions in IL-1β-mediated cell survival response to strain. J Appl Physiol 2011, 110(5):1425-1431.
- [13]Chandrashekar N, Slauterbeck J, Hashemi J: Effects of cyclic loading on the tensile properties of human patellar tendon. Knee 2012, 19(1):65-68.
- [14]Malaviya P, Butler DL, Korvick DL, Proch FS: In vivo tendon forces correlate with activity level and remain bounded: evidence in a rabbit flexor tendon model. J Biomech 1998, 31(11):1043-1049.
- [15]Saber S, Zhang AY, Ki SH, Lindsey DP, Smith RL, Riboh J, Pham H, Chang J: Flexor tendon tissue engineering: bioreactor cyclic strain increases construct strength. Tissue Eng Part A 2010, 16(6):2085-2090.
- [16]Wren TA, Beaupré GS, Carter DR: A model for loading-dependent growth, development, and adaptation of tendons and ligaments. J Biomech 1998, 31(2):107-114.
- [17]Reno C, Marchuk L, Sciore P, Frank CB, Hart DA: Rapid isolation of total RNA from small samples of hypocellular, dense connective tissues. Biotechniques 1997, 22(6):1082-1086.
- [18]Dudli S, Haschtmann D, Ferguson SJ: Fracture of the vertebral endplates, but not equienergetic impact load, promotes disc degeneration in vitro. J Orthop Res 2011, 30(5):809-816.
- [19]Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods 2001, 25(4):402-408.
- [20]Enobakhare BO, Bader DL, Lee DA: Quantification of sulfated glycosaminoglycans in chondrocyte/alginate cultures, by use of 1,9-dimethylmethylene blue. Anal Biochem 1996, 243(1):189-191.
- [21]Farndale RW, Buttle DJ, Barrett AJ: Improved quantitation and discrimination of sulphated glycosaminoglycans by use of dimethylmethylene blue 1. Biochim Biophys Acta 1986, 883(2):173-177.
- [22]Parkinson J, Samiric T, Ilic MZ, Feller JCAA, Handley CJ: Change in proteoglycan metabolism is a characteristic of human patellar tendinopathy. Arthritis Rheum 2010, 62(10):3028-3035.
- [23]Shim JW, Elder SH: Influence of cyclic hydrostatic pressure on fibrocartilaginous metaplasia of achilles tendon fibroblasts. Biomech Model Mechanobiol 2006, 5(4):247-252.
- [24]Leigh DR, Abreu EL, Derwin KA: Changes in gene expression of individual matrix metalloproteinases differ in response to mechanical unloading of tendon fascicles in explant culture. J Orthop Res 2008, 26(10):1306-1312.
- [25]Woon CY, Kraus A, Raghavan SS, Pridgen BC, Megerle K, Pham H, Chang J: Three-dimensional-construct bioreactor conditioning in human tendon tissue engineering. Tissue Eng Part A 2011, 17(19–20):2561-2572.
- [26]White KL, Camire LM, Parks BG, Corey WS, Hinton RY: Krackow locking stitch versus locking premanufactured loop stitch for soft-tissue fixation: a biomechanical study. Arthroscopy 2010, 26(12):1662-1666.
- [27]Nordin M, Frankel VH: Basic biomechanics of the musculoskelettal system. Edited by Butler J. Maryland US: Lippincott Williams & Wilkins; 2001.
- [28]Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P: Molecular biology of the cell. Fourth Edition: Garland; 2002.
- [29]Kjaer M: Role of extracellular matrix in adaptation of tendon and skeletal muscle to mechanical loading. Physiol Rev 2004, 84(2):649-698.
- [30]Scott A, Danielson P, Abraham T, Fong G, Sampaio AV, Underhill TM: Mechanical force modulates scleraxis expression in bioartificial tendons. J Musculoskelet Neuronal Interact 2011, 11(2):124-132.
- [31]Thomopoulos S, Das R, Birman V, Smith L, Ku K, Elson EL, Pryse KM, Marquez JP, Genin GM: Fibrocartilage tissue engineering: the role of the stress environment on cell morphology and matrix expression. Tissue Eng Part A 2011, 17(7–8):1039-1053.
- [32]Maeda T, Sakabe T, Sunaga A, Sakai K, Rivera AL, Keene DR, Sasaki T, Stavnezer E, Iannotti J, Schweitzer R, Ilic D, Baskaran H, Sakai T: Conversion of mechanical force into TGF-β-mediated biochemical signals. Curr Biol 2011, 21(11):933-941.
- [33]Altman GH, Horan RL, Martin I, Farhadi J, Stark PR, Volloch V, Richmond JC, Vunjak-Novakovic G, Kaplan DL: Cell differentiation by mechanical stress. FASEB J 2002, 16(2):270-272.
- [34]Sassoon AA, Ozasa Y, Chikenji T, Sun YL, Larson DR, Maas ML, Zhao C, Jen J, Amadio PC: Skeletal muscle and bone marrow derived stromal cells: A comparison of tenocyte differentiation capabilities. J Orthop Res 2012, 30(11):1710-1718.
- [35]Qi J, Dmochowski JM, Banes AN, Tsuzaki M, Bynum D, Patterson M, Creighton A, Gomez S, Tech K, Cederlund A, Banes AJ: Differential expression and cellular localization of novel isoforms of the tendon biomarker tenomodulin. J Appl Physiol 2012, 113(6):861-871.
- [36]Asundi KR, Rempel DM: Cyclic loading inhibits expression of MMP-3 but not MMP-1 in an in vitro rabbit flexor tendon model. Clin Biomech (Bristol, Avon) 2008, 23(1):117-121.