The role of extracellular matrix elasticity and composition in regulating the nucleus pulposus cell phenotype in the intervertebral disc: A narrative review

Journal of Biomechanical Engineering

Volumn 136, Issue 2, 2014, Pages

  Hwang, Priscilla Y ^a   Chen, Jun ^b   Jing, Liufang ^a   Hoffman, Brenton D ^a   Setton, Lori A ^b  

^a Duke University   (United States)

^b DUKE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CELL INTERACTION; CELL PHENOTYPE; CELLULAR PHENOTYPES; EXTRACELLULAR MATRICES; HEALTH CARE COSTS; INTERVERTEBRAL DISCS; KEY REGULATORS; NUCLEUS PULPOSUS;

CELLS; ELASTICITY; MORPHOLOGY; PATHOLOGY; TISSUE ENGINEERING;

CYTOLOGY;

LAMININ; FIBRILLAR COLLAGEN;

ARTICLE; CELL COMPOSITION; CELL INTERACTION; CELL MATURATION; ELASTICITY; EXTRACELLULAR MATRIX; HUMAN; IMMATURITY; MICROENVIRONMENT; NONHUMAN; NUCLEUS PULPOSUS; PHENOTYPE; PROTEIN INTERACTION; ANIMAL; BIOLOGICAL MODEL; CELL DIFFERENTIATION; COMPUTER SIMULATION; CYTOLOGY; FIBROCARTILAGE; INTERVERTEBRAL DISK; MECHANICAL STRESS; MECHANOTRANSDUCTION; PHYSIOLOGY; YOUNG MODULUS;

ANIMALS; CELL DIFFERENTIATION; COMPUTER SIMULATION; ELASTIC MODULUS; EXTRACELLULAR MATRIX; FIBRILLAR COLLAGENS; FIBROCARTILAGE; HUMANS; INTERVERTEBRAL DISC; MECHANOTRANSDUCTION, CELLULAR; MODELS, BIOLOGICAL; STRESS, MECHANICAL;

EID: 84896752519     PISSN: 01480731     EISSN: 15288951     Source Type: Journal    
DOI: 10.1115/1.4026360     Document Type: Article

References (104)

1. Bogduk, N., 2005, Clinical Anatomy of the Lumbar Spine and Sacrum, Elsevier, New York.
2. Urban, J. P., and Roberts, S., 2003, "Degeneration of the Intervertebral Disc," Arthritis Res. Ther., 5(3), pp. 120-30. (Pubitemid 36849758)
3. Baer A. E., Laursen, T. A., Guilak, F., and Setton, L. A., 2003, "The Micromechanical Environment of Intervertebral Disc Cells Determined by a Finite Deformation, Anisotropic, and Biphasic Finite Element Model," ASME J. Biomech. Eng., 125(1), pp. 1-11. (Pubitemid 36297223)
4. Hsieh, A. H., Wagner, D. R., Cheng, L. Y., and Lotz, J. C., 2005, "Dependence of Mechanical Behavior of the Murine Tail Disc on Regional Material Properties: A Parametric Finite Element Study," ASME J. Biomech. Eng., 127(7), pp. 1158-1167. (Pubitemid 43067271)
5. Cao, L., Guilak, F., and Setton, L. A., 2009, "Pericellular Matrix Mechanics in the Anulus Fibrosus Predicted by a Three-Dimensional Finite Element Model and In Situ Morphology," Cell. Mol. Bioeng., 2(3), pp. 306-319.
6. Jackson, A. R., Huang, C. Y., Brown, M. D., and Gu, W. Y., 2011, "3D Finite Element Analysis of Nutrient Distributions and Cell Viability in the Intervertebral Disc: Effects of Deformation and Degeneration," ASME J. Biomech. Eng., 133(9), p. 091006.
7. Cao, L., Guilak, F., and Setton, L. A., 2011, "Three-Dimensional Finite Element Modeling of Pericellular Matrix and Cell Mechanics in the Nucleus Pulposus of the Intervertebral Disk Based on In Situ Morphology," Biomech. Model Mechanobiol., 10(1), pp. 1-10.
8. Korecki, C. L., MacLean, J. J., and Iatridis, J. C., 2008, "Dynamic Compression Effects on Intervertebral Disc Mechanics and Biology," Spine, 33(13), pp. 1403-1409.
9. Boos, N., Weissbach, S., Rohrbach, H., Weiler, C., Spratt, K.F., and Nerlich, A.G., 2002, "Classification of Age-Related Changes in Lumbar Intervertebral Discs: 2002 Volvo Award in Basic Science," Spine, 27(23), pp. 2631-2644. (Pubitemid 35425317)
10. Liebscher, T., Haefeli, M., Wuertz, K., Nerlich, A.G., and Boos, N., 2011, "Age-Related Variation in Cell Density of Human Lumbar Intervertebral Disc," Spine, 36(2), pp. 153-159.
11. Roberts, S., Evans, H., Trivedi, J., and Menage, J., 2006, "Histology and Pathology of the Human Intervertebral Disc," J. Bone Joint Surg. Am., 88(2), pp. 10-14.
12. Johnson, W. E., Eisenstein, S. M., and Roberts, S., 2001, "Cell Cluster Formation in Degenerate Lumbar Intervertebral Discs is Associated With Increased Disc Cell Proliferation," Connect Tissue Res., 42(3), pp. 197-207. (Pubitemid 33040960)
13. Johnson, W. E., and Roberts, S., 2003, "Human Intervertebral Disc Cell Morphology and Cytoskeletal Composition: A Preliminary Study of Regional Variations in Health and Disease," J. Anat., 203(6), pp. 605-612. (Pubitemid 37509128)
14. Hastreiter, D., Ozuna, R. M., and Spector, M., 2001, "Regional Variations in Certain Cellular Characteristics in Human Lumbar Intervertebral Discs, Including the Presence of Alpha-Smooth Muscle Actin," J. Orthop. Res., 19, pp. 597-604. (Pubitemid 32700974)
15. Choi, K. S., Cohn, M. J., and Harfe, B. D., 2008, "Identification of Nucleus Pulposus Precursor Cells and Notochordal Remnants in the Mouse: Implications for Disk Degeneration and Chordoma Formation," Dev. Dyn., 2008; 237(12), pp. 3953-3958.
16. Roughley, P. J., 2004, "Biology of Intervertebral Disc Aging and Degeneration: Involvement of the Extracellular Matrix," Spine, 29(23), pp. 2691-2699. (Pubitemid 40353255)
17. Urban, J. P., 2002, "The Role of the Physicochemical Environment in Determining Disc Cell Behaviour," Biochem. Soc. Trans., 30(6), pp. 858-864. (Pubitemid 36002367)
18. Johnstone, B., and Bayliss, M. T., 1995, "The Large Proteoglycans of the Human Intervertebral Disc. Changes in Their Biosynthesis and Structure With Age, Topography, and Pathology," Spine, 20(6), pp. 674-684.
19. Nachemson, A., 1992, "Lumbar Mechanics as Revealed by Lumbar Intradiscal Pressure Measurements, The Lumbar Spine and Back Pain, 4th ed., M. I. V. Jayson, Churchill Livingstone, New York, pp. 157-171.
20. McNally, D. S., and Adams, M. A., 1992, "Internal Intervertebral Disc Mechanics as Revealed by Stress Profilometry," Spine, 17, pp. 66-73.
21. Hurri, H., and Karppinen, J., "Discogenic Pain," Pain, 112(3), pp. 225-228.
22. Peacock, A., 1951, Observations on the Prenatal Development of the Intervertebral Disc in Man," J. Anat., 85(3), pp. 260-274.
23. Walmsley, R., 1953, The Development and Growth of the Intervertebral Disc, Edinburgh Med. J., 60(8), pp. 341-364.
24. Ellis, K., Bagwell, J., and Bagnat, M., 2013, "Notochord Vacuoles are Lysosome-Related Organelles That Function in Axis and Spine Morphogenesis," J. Cell. Biol., 200(5), pp. 667-679.
25. Gilchrist, C. L., Chen, J., Richardson, W. J., Loeser, R. F., and Setton, L. A., 2007, "Functional Integrin Subunits Regulating Cell-Matrix Interactions in the Intervertebral Disc," J. Orthop. Res., 25(6), pp. 829-840. (Pubitemid 46831892)
26. Hunter, C. J., Matyas, J. R., and Duncan, N. A., 2003, "The Three-Dimensional Architecture of the Notochordal Nucleus Pulposus: Novel Observations on Cell Structures in the Canine Intervertebral Disc," J. Anat., 202(3), pp. 279-291. (Pubitemid 36503991)
27. Trout, J. J., Buckwalter, J. A., Moore, K. C., and Landas, S. K., 1982, "Ultrastructure of the Human Intervertebral Disc I Changes in Notochordal Cells With Age," Tissue Cell, 14(2), pp. 359-369. (Pubitemid 12021684)
28. Minogue, B. M., Richardson, S.M., Zeef, L. A., Freemont, A. J., and Hoyland, J. A., 2010, "Characterization of the Human Nucleus Pulposus Cell Phenotype and Evaluation of Novel Marker Gene Expression to Define Adult Stem Cell Differentiation," Arthritis Rheum., 62(12), pp. 3695-3705.
29. Gotz, W., Kasper, M., Fischer, G., and Herken, R., 1995, "Intermediate Filament Typing of the Human Embryonic and Fetal Notochord," Cell Tissue Res., 280(2), pp. 455-462.
30. Buxboim, A., Ivanovska, I. L., and Discher, D. E., 2010, "Matrix Elasticity, Cytoskeletal Forces and Physics of the Nucleus: How Deeply do Cells 'Feel' Outside and In?" J. Cell. Sci., 123(3), pp. 297-308.
31. Hayes, A. J., Benjamin, M., and Ralphs, J. R., 1999, "Role of Actin Stress Fibres in the Development of the Intervertebral Disc: Cytoskeletal Control of Extracellular Matrix Assembly," Dev. Dyn., 215(3), pp. 179-189. (Pubitemid 29310066)
32. Lehtonen, E., Stefanovic, V., and Saraga-Babic, M., 1995, "Changes in the Expression of Intermediate Filaments and Desmoplakins During Development of Human Notochord," Differentiation, 59(1), pp. 43-49.
33. Rodrigues-Pinto, R., Richardson, S. M., and Hoyland, J. A., 2013, "Identification of Novel Nucleus Pulposus Markers: Interspecies Variations and Implications for Cell-Based Therapies for Intervertebral Disc Degeneration," Bone Joint Res., 2(8), pp. 169-178.
34. Tang, X., Jing, L., and Chen, J., 2012, "Changes in the Molecular Phenotype of Nucleus Pulposus Cells With Intervertebral Disc Aging," PLoS One, 7(12), pp. e52020-e52020-7.
35. Minogue, B. M., Richardson, S. M., Zeef, L. A., Freemont, A. J., and Hoyland, J. A., 2010, "Transcriptional Profiling of Bovine Intervertebral Disc Cells: Implications for Identification of Normal and Degenerate Human Intervertebral Disc Cell Phenotypes," Arthritis Res. Ther., 12(1), pp. R22-1-R22-20.
36. Lv, F., Leung, V. Y., Huwang, S., Huang, Y., Sun, Y., and Cheung, K. M., 2013, "In Search of Nucleus Pulposus-Specific Molecular Markers," Rheumatology: Advance Access published online: September 18, 2013.
37. Li, S., Duance, V. C., and Blain, E. J., 2008, "Zonal Variations in Cytoskeletal Element Organization, mRNA and Protein Expression in the Intervertebral Disc," J. Anat., 213(6), pp. 725-732.
38. Guilak, F., Ting-Beall, H. P., Baer, A. E., Trickey, W. R., Erickson, G. F., and Setton, L. A., 1999, "Viscoelastic Properties of Intervertebral Disc Cells Identification of Two Biomechanically Distinct Cell Populations," Spine, 24(23), pp. 2475-2483. (Pubitemid 30002984)
39. Gilson, A., Dreger, M., and Urban, J. P., 2010, "Differential Expression Level of Cytokeratin 8 in Cells of the Bovine Nucleus Pulposus Complicates the Search for Specific Intervertebral Disc Cell Markers," Arthritis Res. Ther., 12(1), p. R24.
40. Stosiek, P., Kasper, M., and Karsten, U., 1988, "Expression of Cytokeratin and Vimentin in Nucleus Pulposus Cells," Differentiation, 39(1), pp. 78-81. (Pubitemid 19045796)
41. Hunter, C. J., Matyas, J. R., and Duncan, N. A., 2004, "Cytomorphology of Notochordal and Chondrocytic Cells From the Nucleus Pulposus: A Species Comparison," J. Anat. 205(5), pp. 357-362. (Pubitemid 39642429)
42. Brown, M. J., Hallam, J. A., Colucci-Guyon, E., and Shaw, S., 2001, "Rigidity of Circulating Lymphocytes is Primarily Conferred by Vimentin Intermediate Filaments," J. Immunol., 166(11), pp. 6640-6646. (Pubitemid 32467205)
43. Herrmann, H., Bar, H., Kreplak, L., Strelkov, S.V., and Aebi, U., 2007, "Intermediate Filaments: From Cell Architecture to Nanomechanics," Nat. Rev. Mol. Cell. Biol., 8(7), pp. 562-573. (Pubitemid 46985377)
44. Benjamin, M., Archer, C. W., and Ralphs, J. R., 1994, "Cytoskeleton of Cartilage Cells," Microsc. Res. Tech., 28(5), pp. 372-377. (Pubitemid 24222668)
45. Eggli, P. S., Hunziker, E. B., and Schenk, R. K., 1988, "Quantitation of Structural Features Characterizing Weight-and Less-Weight-Bearing Regions in Articular Cartilage: A Stereological Analysis of Medial Femoral Condyles in Young Adult Rabbits," Anat. Rec., 222(3), pp. 217-227.
46. Chen, J., Yan, W., and Setton, L. A., 2004, "Static Compression Induces Zonal-Specific Changes in Gene Expression for Extracellular Matrix and Cytoskeletal Proteins in Intervertebral Disc Cells In Vitro," Matrix Biol., 22(7), pp. 573-583. (Pubitemid 38283781)
47. Butler, W. F., 1988, "Comparative Anatomy and Development of the Mammalian Disc," The Biology of the Intervertebral Disc, P. Gosh, ed., CRC, Boca Raton, pp. 39-82.
48. Lee, C. R, Sakai, D., Nakai, T., Toyama, K., Mochia, J., Alini, M., and Grad, S., 2007, "A Phenotypic Comparison of Intervertebral Disc and Articular Cartilage Cells in the Rat," Eur. Spine J., 16(12), pp. 2174-2185. (Pubitemid 350276086)
49. Sakai, D., Nakai, T., Mochia, J., Alini, M., and Grad, S., 2009, "Differential Phenotype of Intervertebral Disc Cells: Microarray and Immunohistochemical Analysis of Canine Nucleus Pulposus and Anulus Fibrosus," Spine, 34(14), pp. 1448-1456.
50. Risbud, M. V., Schaer, T. P., and Shapiro, I. M., 2010, "Toward an Understanding of the Role of Notochordal Cells in the Adult Intervertebral Disc: From Discord to Accord," Dev. Dyn., 239(8), pp. 2141-2148.
51. Roberts, S., Ayad, S., and Menage, P. J., 1991, "Immunolocalisation of Type VI Collagen in the Intervertebral Disc," Ann. Rheum. Dis., 50(11), pp. 787-791.
52. Trout, J. J., Buckwalter, J. A., and Moore, K. C., 1982, "Ultrastructure of the Human Intervertebral Disc: II. Cells of the Nucleus Pulposus," Anat. Rec., 204(4), pp. 307-314. (Pubitemid 13225360)
53. Cao, L., Guilak, F., and Setton, L. A., 2007, Three-Dimensional Morphology of the Pericellular Matrix of Intervertebral Disc Cells in the Rat," J. Anat., 211(4), pp. 444-452. (Pubitemid 47456832)
54. Errington, R. J., Puustjarvi, K., White, I. R., Roberts, S., Urban, J. P., 1998, "Characterisation of Cytoplasm-Filled Processes in Cells of the Intervertebral Disc," J. Anat., 192(3), pp. 369-378. (Pubitemid 28331809)
55. Iatridis, J. C., Setton, L. A., Weidenbaum, M., and Mow, V. C., 1997, "The Viscoelastic Behavior of the Non-Degenerate Human Lumbar Nucleus Pulposus in Shear," J. Biomech., 30(10), pp. 1005-1013. (Pubitemid 27490229)
56. Iatridis, J. C, Weidenbaum, M., Setton, L. A., and Mow, V. C., 1996, "Is the Nucleus Pulposus a Solid or a Fluid? Mechanical Behaviors of the Nucleus Pulposus of the Human Intervertebral Disc," Spine, 21(10), pp. 1174-1184. (Pubitemid 26161382)
57. Cloyd, J. M., Malhotra, N. R., Weng, L., Chen, W., Mauck, R. L., and Elliott, D. M., 2007, Material Properties in Unconfined Compression of Human Nucleus Pulposus, Injectable Hyaluronic Acid-Based Hydrogels and Tissue Engineering Scaffolds," Eur Spine J., 16(11), pp. 1892-1898 (Pubitemid 350105326)
58. Eyre, D. R., and Muir, H., 1977, "Quantitative Analysis of Types I and II Collagens in Human Intervertebral Discs at Various Ages," Biochim. Biophys. Acta. 492(1), pp. 29-42. (Pubitemid 8106166)
59. Gower, W. E., and Pedrini, V., 1969, "Age-Related Variations in Proteinpolysaccharides From Human Nucleus Pulposus, Annulus Fibrosus, and Costal Cartilage," J Bone Joint Surg. Am., 51(6), pp. 1154-1162.
60. Taylor, J. R., and Twomey, L. T., 1988, "The Development of the Human Intervertebral Disc," The Biology of the Intervertebral Disc, P. Gosh, ed., CRC, Boca Raton, FL., pp. 39-82.
61. Roberts, S., Menage, J., Duance, V., Wotton, S., and Ayad, S., 1991, "Volvo Award in Basic Sciences Collagen Types Around the Cells of the Intervertebral Disc and Cartilage End Plate: An Immunolocalization Study," Spine, 16(9), pp. 1030-1038.
62. Melrose, J., Ghosh, P., and Taylor, T. K., 2001, "A Comparative Analysis of the Differential Spatial and Temporal Distributions of the Large (Aggrecan, Versican) and Small (Decorin, Biglycan, Fibromodulin) Proteoglycans of the Intervertebral Disc," J. Anat., 198(1), pp. 3-15. (Pubitemid 32162312)
63. Yu, J., 2002, "Elastic Tissues of the Intervertebral Disc," Biochem. Soc. Trans, 30(6), pp. 848-852. (Pubitemid 36002365)
64. Chen, J., Jing, L., Gilchrist, C. L., Richardson, W. J., Fitch, R. D., and Setton, L. A., 2009, "Expression of Laminin Isoforms, Receptors and Binding Proteins Unique to Nucleus Pulposus Cells of Immature Intervertebral Disc," Connect Tissue Res., 50, pp. 294-306.
65. Nettles, D. L., Richardson, W. J., and Setton, L. A., 2004, "Integrin Expression in Cells of the Intervertebral Disc," J. Anat. 204(6), pp. 515-520. (Pubitemid 38807813)
66. Natarajan, R. N., Williams, J. R., and Andersson, G. B., 2004, "Recent Advances in Analytical Modeling of Lumbar Disc Degeneration," Spine, 29(23), pp. 2733-2741. (Pubitemid 40353259)
67. Discher, D. E., Janmey, P., and Wang, Y. L., 2005, "Tissue Cells Feel and Respond to the Stiffness of Their Substrate," Science, 310(5751), pp. 1139-1143. (Pubitemid 41681732)
68. Pelham, R. J., Jr., and Wang, Y., 1997, "Cell Locomotion and Focal Adhesions are Regulated by Substrate Flexibility," Proc. Natl. Acad. Sci. U.S.A, 94(25), pp. 13661-5. (Pubitemid 28009639)
69. Guo, W. H., Frey, M. T., Burnham, N. A., and Wang, Y. L., 2006, "Substrate Rigidity Regulates the Formation and Maintenance of Tissues," Biophys. J., 90(6), pp. 2213-2220.
70. Gilchrist., C. L., Darling, E. M., Chen, J., and Setton, L. A., 2011, "Extracellular Matrix Ligand and Stiffness Modulate Immature Nucleus Pulposus Cell-Cell Interactions," PLoS One, 6(11), pp. e27170-1-e27170-9.
71. Johannessen, W., and Elliott, D. M., 2005, "Effects of Degeneration on the Biphasic Material Properties of Human Nucleus Pulposus in Confined Compression," Spine, 30(24), pp. E724-E729. (Pubitemid 43011027)
72. Iatridis, J. C., Setton, L. A., Weidenbaum, M., and Mow, V. S., 1997, "Alterations in the Mechanical Behavior of the Human Lumbar Nucleus Pulposus With Degeneration and Aging," J. Orthop. Res., 15(2), pp. 318-322. (Pubitemid 27220553)
73. Miner, J. H., and Yurchenco, P. D., 2004, "Laminin Functions in Tissue Morphogenesis," Annu. Rev. Cell. Dev. Biol., 20, pp. 255-284. (Pubitemid 39488639)
74. Zaidel-Bar, R,. Shalev, I., Ma'ayan A., Iyengar, R., Geiger, B., 2007, "Functional Atlas of the Integrin Adhesome," Nat. Cell. Biol., 9(8), pp. 858-867. (Pubitemid 47190436)
75. Hoffman, B. D., Grashoff, C., and Schwartz, M. A., 2011, "Dynamic Molecular ProcessesMediate Cellular Mechanotransduction," Nature, 475(7356), pp. 316-323.
76. Hynes, R. O., 1992, "Integrins: Versatility, Modulation, and Signaling in Cell Adhesion," Cell, 69(1), pp. 11-25.
77. Schwartz, M. A., 2010, "Integrins and Extracellular Matrix in Mechanotransduction," Cold Spring Harb. Perspect. Biol., 2(12), pp. a005066-1-a005066-13.
78. Bridgen, D. T., Gilchrist, C. L., Richardson, W. J., Isaacs, R. E., Brown, C. R., Yang, K. L., Chen, J., and Setton, L. A., 2013, "Integrin-Mediated Interactions With Extracellular Matrix Proteins for Nucleus Pulposus Cells of the Human Intervertebral Disc,". J. Orthop. Res., 31(10), pp. 1661-1667.
79. Le Maitre, C. L., Frain, J., Millward-Sadler, J., Fotheringham, A. P., Freemont, A. J., and Hoyland, J. A., 2009, "Altered Integrin Mechanotransduction in Human Nucleus Pulposus Cells Derived From Degenerated Discs," Arthritis Rheum., 60(2), pp. 460-469.
80. Anderson, D. G., Li, X., and Balian, G., 2005, "A Fibronectin Fragment Alters the Metabolism by Rabbit Intervertebral Disc Cells in vitro," Spine, 30(11), pp. 1242-1246. (Pubitemid 40791318)
81. Aota, Y., An, H. S., Homandberg, G., Thonar, E. J., Andersson, G. B., Pichika, R., and Masuda, K., 2005, "Differential Effects of Fibronectin Fragment on Proteoglycan Metabolism by Intervertebral Disc Cells: A Comparison With Articular Chondrocytes," Spine, 30(7), pp. 722-728.
82. Chen, J., Yan, W., and Setton, L. A., 2006, "Molecular Phenotypes of Notochordal Cells Purified From Immature Nucleus Pulposus," Eur. Spine J., 15(3), pp. S303-S311. (Pubitemid 44371007)
83. Gilchrist, C. L., Francisco, A. T., Plopper, G. E., Chen, J., and Setton, L. A., 2011, "Nucleus Pulposus Cell-Matrix Interactions With Laminins," Eur. Cell. Mater, 21, pp. 523-532.
84. Wang, Y. L., and Pelham, R. J., Jr., 1998, "Preparation of a Flexible, Porous Polyacrylamide Substrate for Mechanical Studies of Cultured Cells," Methods Enzymol., 298, pp. 489-496. (Pubitemid 28450775)
85. Hassell, J. R., Robey, P. G., Barrach, H. J., Wilczek, J., Rennard, S. I., and Martin, G. F., 1980, "Isolation of a Heparan Sulfate-Containing Proteoglycan From Basement Membrane," Proc. Natl. Acad. Sci. U.S.A., 77(8), pp. 4494-4498.
86. Zhang, Y.H., Zhao, C.Q., Jiang, L.S., and Dai, L.Y., 2011, "Substrate Stiffness Regulates Apoptosis and the mRNA Expression of Extracellular Matrix Regulatory Genes in the Rat Annular Cells," Matrix Biol., 30(2), pp. 135-144.
87. Engler, A. J., Sen, S., Sweeney, H. L., and Discher, D. E., 2006, "Matrix Elasticity Directs Stem Cell Lineage Specification," Cell, 126(4) pp. 677-689. (Pubitemid 44233625)
88. Yeung, T., Georges, P. C., Flanagan, L. A., Marg, B., Ortiz, M., Funaki, M., Zahir, N., Ming, W., Weaver, V., and Janmey, P. A., 2005, "Effects of Substrate Stiffness on Cell Morphology, Cytoskeletal Structure, and Adhesion," Cell. Motil. Cytoskeleton, 60(1), pp. 24-34. (Pubitemid 40066224)
89. Wang, H. B., Dembo, M., and Wang, Y. L., 2000, "Substrate Flexibility Regulates Growth and Apoptosis of Normal but not Transformed Cells," Am. J. Physiol. Cell. Physiol., 279(5), pp. C1345-C1350.
90. Weber, G. F., Bjerke, M. A., and DeSimone, D. W., 2011, "Integrins and Cadherins Join Forces to Form Adhesive Networks," J. Cell. Sci., 124(8), pp. 1183-1193.
91. Schwartz, M. A., and DeSimone, D. W., 2008, "Cell Adhesion Receptors in Mechanotransduction," Curr. Opin. Cell. Biol., 20(5), pp. 551-556.
92. Braga, V. M., 2002, "Cell-Cell Adhesion and Signalling," Curr. Opin. Cell. Biol., 14(5), pp. 546-556. (Pubitemid 35247736)
93. Arthur, W. T., Noren, N. K., and Burridge, K., 2002, "Regulation of Rho Family GTPases by Cell-Cell and Cell-Matrix Adhesion," Biol. Res., 35(2), pp. 239-246. (Pubitemid 35189798)
94. Amano, M., Ito, M., Kimura, K., Fukata, Y., Chihara, K., Nakano, T., Matsuura, Y., and Kaibuchi, K., 1996, "Phosphorylation and Activation of Myosin by Rho-Associated Kinase (Rho-Kinase)," J. Biol. Chem., 271(34), pp. 20246-20249. (Pubitemid 26281788)
95. Amano, M., Chihara, K., Kazushi, K., Fukata, Y., Nakamura, N., Matsuura, Y., and Kaibuchi, K., 1997, "Formation of Actin Stress Fibers and Focal Adhesions Enhanced by Rho-Kinase," Science, 275(5304), pp. 1308-1311. (Pubitemid 27114159)
96. Kimura, K., Ito, M., Amano, M., Chihara, K., Fukata, Y., Nakafuku, M., Yamamori, B., Feng, J., Nakano, T., Okawa, K., Iwamatsu, A., and Kaibuchi, K., 1996, Regulation of Myosin Phosphatase by Rho and Rho-Associated Kinase (Rho-Kinase), Science, 273(5272), pp. 245-248. (Pubitemid 26285892)
97. Hall, A., 2005, "Rho GTPases and the Control of Cell Behaviour," Biochem. Soc. Trans., 33(5), pp. 891-895. (Pubitemid 41659073)
98. Burridge, K., and Wennerberg, K., 2004, "Rho and Rac Take Center Stage," Cell, 116(2), pp. 167-179. (Pubitemid 38167310)
99. Yamada, S., and Nelson, W. J., 2007, "Localized Zones of Rho and Rac Activities Drive Initiation and Expansion of Epithelial Cell-Cell Adhesion," J. Cell. Biol., 178(3), pp. 517-527. (Pubitemid 47196158)
100. Noren, N. K., Niessen, C. M., Gumbiner, B. M., and Burridge, K., 2001, "Cadherin Engagement Regulates Rho Family GTPases," J. Biol. Chem., 276(36), pp. 33305-33308.
101. Fujita, N., Miyamoto, T., Imai, J., Hosogane, N., Suzuki, T., Yagi, M., Morita, K., Ninomiya, K., Miyamoto, K., Takaishi, H., Matsumoto, M., Morioka, H., Yabe, H., Chiba, K., Watanabe, S., Toyama, Y., and Suda, T., 2005, "CD24 is Expressed Specifically in the Nucleus Pulposus of Intervertebral Discs," Biochem Biophys Res Commun, 338(4), pp. 1890-1896. (Pubitemid 41643106)
102. Tang, X. J. L., Setton, L. A., Richardson, W. J., Isaacs, R. E., Fitch, R. D., Brown, C. R., and Chen, J., 2013, "Identifying the Molecular Phenotype of Cells in the Human Intervertebral Disc Reveals the Existence of a Unique Notochordal-Like Cell Population," Trans. Orthop. Res. Soc., 38(859), p. 0859.
103. Weiler, C., Nerlich, A.G., Schaaf, R., Bachmeier, B.E., Wuertz, K., and Boos, N., 2010, "Immunohistochemical Identification of Notochordal Markers in Cells in the Aging Human Lumbar Intervertebral Disc," Eur. Spine J., 19(10), pp. 1761-170.
104. Nerlich, A. G., Schleicher, E. D., and Boos, N., 1997, "Volvo Award Winner in Basic Science Studies. Immunohistologic Markers for Age-Related Changes of Human Lumbar Intervertebral Discs," Spine, 22(24), pp. 2781-2795. (Pubitemid 28070623)