| 研究生: |
羅方妤 Lo, Fang-Yu |
|---|---|
| 論文名稱: |
細胞形狀調控肌腱分化 Shape control of tenogenesis |
| 指導教授: |
王仰高
Wang, Yang-Kao |
| 學位類別: |
碩士 Master |
| 系所名稱: |
醫學院 - 細胞生物與解剖學研究所 Institute of Cell Biology and Anatomy |
| 論文出版年: | 2017 |
| 畢業學年度: | 105 |
| 語文別: | 英文 |
| 論文頁數: | 63 |
| 中文關鍵詞: | 肌腱分化 、細胞形狀 |
| 外文關鍵詞: | Tenogenesis, cell shape |
| 相關次數: | 點閱:101 下載:6 |
| 分享至: |
| 查詢本校圖書館目錄 查詢臺灣博碩士論文知識加值系統 勘誤回報 |
肌腱是一種收縮性結締組織,連接肌肉以及骨頭之間,以幫助關節的活動。過度使
用以及不正常的修復經常造成慢性發炎而引發疼痛以及行動不便。因此,肌腱再生被
認為是最具有潛能的治療方式。傳統上可以使用生長因子幫助肌腱再生以及修復,除
此之外越來越多的研究顯示肌腱微環境中的物理因子的改變也可能誘導肌腱分化,例
如改變細胞的形狀以及調整胞外基質軟硬度。而傳統的細胞生物學方法,並無法有效
的改變細胞的形狀。微轉印技術可以控制細胞的形狀和大小,且此技術已經廣泛的應
用於細胞組織工程。許多研究也證實微轉印技術可以幫助幹細胞分化成不同的細胞。
因此在本研究中我們欲探討是否能利用生醫微製程中之微轉印技術,透過改變細胞形
狀而影響肌腱分化。首先我們先確認我們使用的肌腱前驅幹細胞是否具有幹細胞的特
性,結果顯示肌腱前驅細胞可表現與間質幹細胞相似的表面抗原,同時也具有生長與
多功分化的潛能。接著我們利用胞外基質覆蓋的線行微轉印圖形建立肌腱分化的系統。
我們利用免疫染色的方法檢視SCX 以及TNMD 的表現,以評估肌腱分化的結果。
結果顯示:透過線型微轉印技術可以成功的誘導肌腱的分化,同時我們也發現分化的
細胞會有較高的核長寬比以及較小的核面積。除此之外我們使用不同長寬比的微轉印
圖形,發現在拉長的細胞較容易分化成肌腱細胞。接著我們想探討分子的機轉,我們
發現Rho A 蛋白激酶、肌凝蛋白以及肌動蛋白的抑制劑都會阻斷細胞骨架的排列進
而降低肌腱細胞分化的能力,同時我們也以核糖核酸干擾技術將β1 整合素做敲減,
以及使用局部粘著斑激酶阻斷劑降低局部粘著的活性,與上述會得到類似的結果,顯
示微環境中細胞形狀的改變會影響肌腱細胞的分化。在未來的研究,我們希望能夠更
進一部探討細胞形狀是如何透過分子的機轉去促進肌腱的分化能力,而這項研究或許
能夠證實調控細胞形狀可以幫助肌腱的再生醫學的發展
Tendon tissues are highly prone to injury, often resulting in the development of
tendinopathy. Therefore, tendon regeneration has emerged as promising therapeutic
strategy for tendinopathy. The classic method to control tendon cell differentiation is
the application of soluble factors to wound site for healing and induction of tendon
repair. In addition to these soluble cues, growing evidence has implied physical cues,
such as geometric control, is capable of directing stem cell commitment to tendon
lineage. Unfortunately, there is no available biomedical tool which can properly
control cell shape without disturbing other cellular behavior. One of the methods to
control cell geometry is micropatterning, which has been widely used to control cell
shape to regulate stem cell fate. We therefore, hypothesize that changes of cell shape
regulate tenogenesis. To confirm this hypothesis, we performed tendon stem
progenitor cells (TSPCs) to establish tenogenesis in extracellular matrix-coated line
patterning to investigate tenogenesis by different geometric controls in vitro. We
found that TSPCs exhibited proliferation ability and expressed surface markers which
were similar to mesenchymal cells. These TSPCs grown on 20-100/50-100 μm line
pattern expressed tendon markers scleraxis (SCX) and tenomodulin (TNMD) without
soluble factor stimulation. TSPCs grown on line pattern showed decreased nucleus
area and increased aspect ratio. To further elucidate the molecular mechanisms, we
found that Rho kinase inhibitor Y27632, actin cytoskeleton inhibitors cytochalasin D,
and myosin inhibitor blebbistatin, disrupted the F-actin organization and hampered
SCX and TNMD expression in TSPCs on line pattern, suggesting an involvement of Rho-mediated actin organization in tenogenic differentiation. Lastly, using
microppatterned surface with different aspect ratios, we discovered that tenogenesis
was found in elongated cells. More importantly, integrin signaling also played
significant roles in tenogenesis via manipulating integrin b1 expression and inhibition
of focal adhesion kinase activity. Together, this microenvironmental cue can regulate
TSPC tenogenesis and may provide us a basic understanding of how geometry
controls tenogenesis.
Abate, M., Gravare-Silbernagel, K., Siljeholm, C., Iorio, A., Amicis, D., Salini, V., Werner,
S., & Paganelli, R. (2009). Pathogenesis of tendinopathies: inflammation or
degeneration? Arthritis Research & Therapy, 11(3), 235.
Alberton, P., Dex, S., Popov, C., Shukunami, C., Schieker, M., & Docheva, D. (2015). Loss
of tenomodulin results in reduced self-renewal and augmented senescence of
tendon stem/progenitor cells. Stem Cells and Development, 24(5), 597-609.
Andres, B. M., & Murrell, G. A. C. (2008). Treatment of Tendinopathy: What works, what
does not, and what is on the horizon. clinical orthopaedics and related Research,
466(7), 1539-1554.
Arnsdorf, E. J., Tummala, P., Kwon, R. Y., & Jacobs, C. R. (2009). Mechanically induced
osteogenic differentiation--the role of RhoA, ROCKII and cytoskeletal dynamics.
Journal of Cell Science, 122(Pt 4), 546-553.
Attali, R., Warwar, N., Israel, A., Gurt, I., McNally, E., Puckelwartz, M., Glick, B., Nevo,
Y., Ben-Neriah, Z., & Melki, J. (2009). Mutation of SYNE-1, encoding an essential
component of the nuclear lamina, is responsible for autosomal recessive
arthrogryposis. Human Molecular Genetics, 18(18), 3462-3469.
Bell, R., Boniello, M. R., Gendron, N. R., Flatow, E. L., & Andarawis-Puri, N. (2015).
Delayed exercise promotes remodeling in sub-rupture fatigue damaged tendons.
Journal of Orthopaedic Research, 33(6), 919-925.
Bi, Y., Ehirchiou, D., Kilts, T. M., Inkson, C. A., Embree, M. C., Sonoyama, W., Li, L.,
Leet, A. I., Seo, B.M., Zhang, L., Shi, S., & Young, M. F. (2007). Identification of
tendon stem/progenitor cells and the role of the extracellular matrix in their niche.
Nature Medicine, 13(10), 1219-1227.
Boudreau, N. J., & Jones, P. L. (1999). Extracellular matrix and integrin signalling: the
shape of things to come. The Biochemical Journal, 339 ( Pt 3), 481-488.
Brandau, O., Meindl, A., Fässler, R., Aszódi, A., Brandau, O., Meindl, A., Fässler, R., &
Aszódi, A. (2001). A novel gene, tendin, is strongly expressed in tendons and
ligaments and shows high homology with chondromodulin-I. Developmental
Dynamics. 221(1), 72-80
Campbell, I. D., & Humphries, M. J. (2011). Integrin Structure, Activation, and
Interactions. Cold Spring Harbor Perspectives in Biology, 3(3), pii: a004994
Chahal, J., Thiel, G. S., Mall, N., Heard, W., Bach, B. R., Cole, B. J., Nicholson, G. P.,
Verma, N. N., Whelan, D. B., & Romeo, A. A. (2012). The Role of Platelet-Rich
Plasma in Arthroscopic Rotator Cuff Repair: A Systematic Review With
Quantitative Synthesis. Arthroscopy: The Journal of Arthroscopic & Related
Surgery, 28(11), 1718-1727.
Charrasse, S., Meriane, M., Comunale, F., Blangy, A., & Gauthier-Rouvière, C. (2002). Ncadherin–
dependent cell–cell contact regulates Rho GTPases and β-catenin
localization in mouse C2C12 myoblasts. The Journal of Cell Biology, 158(5), 953-
965.
Chen, Yin, Z., Chen, J.L., Shen, W.l., Liu, H.H., Tang, Q.M., Fang, Z., Lu, L.R., J, J., &
Ouyang, H.W. (2012). Force and scleraxis synergistically promote the commitment
of human ES cells derived MSCs to tenocytes. Scientific Reports, 2, 977.
Chen, C. S., Alonso, J. L., Ostuni, E., Whitesides, G. M., & Ingber, D. E. (2003). Cell
shape provides global control of focal adhesion assembly. Biochemical and
Biophysical Research Communications, 307(2), 355-361.
Chen, C. S., Tan, J., & Tien, J. (2004). Mechanotransduction at cell-matrix and cell-cell
contacts. Annual Review of Biomedical Engineering, 6, 275-302.
Chen, L., Liu, J. P., Tang, K. L., Wang, Q., Wang, G. D., Cai, X. H., & Liu, X. M. (2014).
Tendon derived stem cells promote platelet-rich plasma healing in collagenaseinduced
rat achilles tendinopathy. Cellular Physiology and Biochemistry, 34(6),
2153-2168.
Chen, X., Yin, Z., Chen, J.L., Shen, W.L., Liu, H.H., Tang, Q.M., Fang, Z., Lu, L.R., Ji, J.,
& Ouyang, H.W. (2012). Force and scleraxis synergistically promote the
commitment of human ES cells derived MSCs to tenocytes. Scientific Reports, 2,
977.
Chrzanowska-Wodnicka, M., & Burridge, K. (1996). Rho-stimulated contractility drives
the formation of stress fibers and focal adhesions. The Journal of Cell Biology.
141(2), 539-51
DeMali, K. A., & Burridge, K. (2003). Coupling membrane protrusion and cell adhesion.
Journal of Cell Science. 116(pt12), 2389-97.
Deschaseaux, F., & Charbord, P. (2000). Human marrow stromal precursors are alpha 1
integrin subunit-positive. Journal of Cellular Physiology, 184(3), 319-325.
Dhawan, J., & Helfman, D. M. (2004). Modulation of acto-myosin contractility in skeletal
muscle myoblasts uncouples growth arrest from differentiation. Journal of Cell
Science. 117(17),3735-48.
Docheva, D., Hunziker, E. B., Fässler, R., & Brandau, O. (2005). Tenomodulin Is
Necessary for Tenocyte Proliferation and Tendon Maturation. Molecular Cell
Biology, 25(2), 699-705.
Docheva, D., Hunziker, E. B., Fässler, R., Brandau, O., Docheva, D., Hunziker, E. B.,
Fässler, R., & Brandau, O. (2005). Tenomodulin Is Necessary for Tenocyte
Proliferation and Tendon Maturation. Molecular Cell Biology. 25(2), 699-705
Du, J., Chen, X., Liang, X., Zhang, G., Xu, J., He, L., Zhan, Q., Feng, X.-Q., Chien, S., &
Yang, C. (2011). Integrin activation and internalization on soft ECM as a
mechanism of induction of stem cell differentiation by ECM elasticity. Proceedings
of the National Academy of Sciences, 108(23), 9466-9471.
Du, J., Zu, Y., Li, J., Du, S., Xu, Y., Zhang, L., Jiang, L., Wang, Z., Chien, S., & Yang, C.
(2016). Extracellular matrix stiffness dictates Wnt expression through integrin
pathway. Scientific Reports, 6(1), 20395.
Engler, A. J., Sen, S., Sweeney, L. H., & Discher, D. E. (2006). Matrix Elasticity Directs
Stem Cell Lineage Specification. Cell, 126(4), 677-689.
Evans, C. H. (2011). Barriers to the Clinical Translation of Orthopedic Tissue Engineering.
Tissue Engineering Part B: Reviews, 17(6), 437-441.
Fu, J., Wang, Y.K., Yang, M. T., Desai, R. A., Yu, X., Liu, Z., & Chen, C. S. (2011).
Mechanical regulation of cell function with geometrically modulated elastomeric
substrates. Nature Methods, 7(9), 733-736.
Gao, L., McBeath, R., Chen, C. S., Gao, L., McBeath, R., & Chen, C. S. (2010). Stem Cell
Shape Regulates a Chondrogenic Versus Myogenic Fate Through Rac1 and NCadherin.
Stem Cells. 28(3), 564-72.
Garner, W. L., McDonald, J. A., Koo, M., Kuhn, C., 3rd, & Weeks, P. M. (1989).
Identification of the collagen-producing cells in healing flexor tendons. Plastic and
Reconstructive Surgery, 83(5), 875-879.
Geiger, B., Bershadsky, A., Pankov, R., & Yamada, K. M. (2001). Transmembrane
crosstalk between the extracellular matrix--cytoskeleton crosstalk. Nature reviews.
Molecular Cell Biology, 2(11), 793-805.
Gelberman, R. H., Siegel, D. B., Woo, S. L., Amiel, D., Takai, S., & Lee, D. (1991).
Healing of digital flexor tendons: importance of the interval from injury to repair. A
biomechanical, biochemical, and morphological study in dogs. Jounal of Bone and
Joint Surgury, 73(1), 66-75.Gronthos, S., Zannettino, A. C. W., Hay, S. J., Shi, S., Graves, S. E., Kortesidis, A., &
Simmons, P. J. (2003). Molecular and cellular characterisation of highly purified
stromal stem cells derived from human bone marrow. Journal of Cell Science,
116(9), 1827-1835.
Grove, J. R. (2008). Autograft, allograft and xenograft options in the treatment of neglected
achilles tendon ruptures: a historical review with illustration of surgical repair. The
Foot & Ankle Journal, 1(5). 1
Heo, S.J., Driscoll, T. P., Thorpe, S. D., Nerurkar, N. L., Baker, B. M., Yang, M. T., Chen,
C. S., Lee, D. A., & Mauck, R. L. (2016). Differentiation alters stem cell nuclear
architecture, mechanics, and mechano-sensitivity. eLife, 5.
Higuchi, A., Ling, Q.D. D., Chang, Y., Hsu, S.T. T., & Umezawa, A. (2013). Physical cues
of biomaterials guide stem cell differentiation fate. Chemical Reviews, 113(5),
3297-3328.
Hill, C. S., Wynne, J., & Treisman, R. (1995). The Rho family GTPases RhoA, Rac1, and
CDC42Hs regulate transcriptional activation by SRF. Cell, 81(7), 1159-1170.
Hocking, D. C., Sottile, J., & McKeown-Longo, P. J. (1998). Activation of distinct
alpha5beta1-mediated signaling pathways by fibronectin's cell adhesion and matrix
assembly domains. The Journal of Cell Biology, 141(1), 241-253.
Hu, J. J., Yin, Z., Shen, W. L., Xie, Y. B., Zhu, T., Lu, P., Cai, Y. Z., Kong, M. J., Heng, B.,
Zhou, Y. T., Chen, W. S., Chen, X., & Ouyang, H. W. (2016). Pharmacological
Regulation of In Situ Tissue Stem Cells Differentiation for Soft Tissue Calcification
Treatment. Stem Cells, 34(4), 1083-1096.
Huveneers, S., & Danen, E. H. J. (2009). Adhesion signaling – crosstalk between integrins,
Src and Rho. Journal of Cell Science, 122(8), 1059-1069.
Hynes, R. O. (2002). Integrins: bidirectional, allosteric signaling machines. Cell, 110(6),673-687.
Ingber, D. E. (2006). Mechanical control of tissue morphogenesis during embryological
development. The International journal of Developmental Biology, 50(2-3), 255-
266.
Khan, K. M., Cook, J. L., Bonar, F., Harcourt, P., & Astrom, M. (1999). Histopathology of
common tendinopathies. Update and implications for clinical management. Sports
Medine, 27(6), 393-408.
Khatau, S. B., Hale, C. M., Stewart-Hutchinson, P. J., Patel, M. S., Stewart, C. L., Searson,
P. C., Hodzic, D., & Wirtz, D. (2009). A perinuclear actin cap regulates nuclear
shape. Proceedings of the National Academy of Sciences of the United States of
America, 106(45), 19017-19022.
Kilian, K. A., Bugarija, B., Lahn, B. T., & Mrksich, M. (2010). Geometric cues for
directing the differentiation of mesenchymal stem cells. Proceedings of the
National Academy of Sciences of the United States of America, 107(11), 4872-
4877.
Kim, S.J. J., Lee, J. K., Kim, J. W., Jung, J.W. W., Seo, K., Park, S.B. B., Roh, K.H. H.,
Lee, S.R. R., Hong, Y. H., Kim, S. J., Lee, Y.S. S., Kim, S. J., & Kang, K.-S. S.
(2008). Surface modification of polydimethylsiloxane (PDMS) induced
proliferation and neural-like cells differentiation of umbilical cord blood-derived
mesenchymal stem cells. Journal of materials science. Materials in Medicine, 19(8),
2953-2962.
Kirchgesner, T., Larbi, A., Omoumi, P., Malghem, J., Zamali, N., Manelfe, J., Lecouvet, F.,
Berg, B., Djebbar, S., & Dallaudière, B. (2014). Drug-induced tendinopathy: From
physiology to clinical applications. Joint Bone Spine, 81(6), 485-492.
Klepps, S., Bishop, J., Lin, J., Cahlon, O., Strauss, A., Hayes, P., & Flatow, E. L. (2004).Prospective Evaluation of the Effect of Rotator Cuff Integrity on the Outcome of
Open Rotator Cuff Repairs. American Journal of Sports Medicine, 32(7), 1716-
1722.
Knobloch, K. (2008). The role of tendon microcirculation in Achilles and patellar
tendinopathy. Journal of Orthopaedic Surgery and Research, 3(1), 1-13.
Kozma, R., Ahmed, S., Best, A., & Lim, L. (1995). The Ras-related protein Cdc42Hs and
bradykinin promote formation of peripheral actin microspikes and filopodia in
Swiss 3T3 fibroblasts. Molecular Cell Biology, 15(4), 1942-1952.
Krueger-Franke, M., Siebert, C. H., & Scherzer, S. (1995). Surgical treatment of ruptures
of the Achilles tendon: a review of long-term results. British Journal of Sports
Medicine, 29(2), 121-125.
Lee, J., Abdeen, A. A., & Kilian, K. A. (2014). Rewiring mesenchymal stem cell lineage
specification by switching the biophysical microenvironment. Scientific Reports,
4(1), 5188.
Lee, J., Abdeen, A. A., Tang, X., Saif, T. A., & Kilian, K. A. (2015). Geometric guidance of
integrin mediated traction stress during stem cell differentiation. Biomaterials, 69,
174-183.
Lehnert, D., Wehrle-Haller, B., David, C., Weiland, U., Ballestrem, C., Imhof, B. A., &
Bastmeyer, M. (2004). Cell behaviour on micropatterned substrata: limits of
extracellular matrix geometry for spreading and adhesion. Journal of Cell Science,
117(1), 41-52.
Lejard, Blais, F., Guerquin, M.J., Bonnet, A., Bonnin, M.A., Havis, E., Malbouyres, M.,
Bidaud, C., Maro, G., Gilardi-Hebenstreit, P., Rossert, J., Ruggiero, F., & Duprez,
D. (2011). EGR1 and EGR2 Involvement in Vertebrate Tendon Differentiation.
Journal of Biological Chemistry, 286(7), 5855-5867
Lejard, V., Blais, F., Guerquin, M. J., Bonnet, A., Bonnin, M. A., Havis, E., Malbouyres,
M., Bidaud, C. B., Maro, G., Gilardi-Hebenstreit, P., Rossert, J., Ruggiero, F., &
Duprez, D. (2011). EGR1 and EGR2 involvement in vertebrate tendon
differentiation. Journal of Biological Chemistry, 286(7), 5855-5867.
Li, H., Wen, F., Wong, Y. S., Boey, F. Y., Subbu, V. S., Leong, D. T., Ng, K. W., Ng, G. K.,
& Tan, L. P. (2012). Direct laser machining-induced topographic pattern promotes
up-regulation of myogenic markers in human mesenchymal stem cells. Acta
Biomaterialia, 8(2), 531-539.
Li, H.Y., & Hua, Y.H. (2016). Achilles Tendinopathy: Current concepts about the basic
science and clinical treatments. BioMed Research International, 2016, 1-9.
Libotte, T., Zaim, H., & Abraham, S. (2005). Lamin A/C–dependent localization of
Nesprin-2, a giant scaffolder at the nuclear envelope. Molecular Biology of the
Cell. 16(7), 3411-24
Liu, Al-Shaikh, R. A., Panossian, V., Finerman, G. A., & Lane, J. M. (1997). Estrogen
affects the cellular metabolism of the anterior cruciate ligament. A potential
explanation for female athletic injury. American Journal of Sports Medicine, 25(5),
704-709.
Liu, C.F., Aschbacher-Smith, L., Barthelery, N. J., Dyment, N., Butler, D., & Wylie, C.
(2011). What we should know before using tissue engineering techniques to repair
injured tendons: a developmental biology perspective. Tissue Engineering. Part B,
Reviews, 17(3), 165-176.
Liu, H., Zhang, C., Zhu, S., Lu, P., Zhu, T., Gong, X., Zhang, Z., Hu, J., Yin, Z., Heng, B.
C., Chen, X., & Ouyang, H. W. (2015). Mohawk promotes the tenogenesis of
mesenchymal stem cells through activation of the TGFβ signaling pathway. Stem
Cells, 33(2), 443-455.Liu, J., Tao, X., Chen, L., Han, W., Zhou, Y., & Tang, K. (2015). CTGF positively regulates
BMP12 induced tenogenic differentiation of tendon stem cells and signaling.
Cellular Physiology and Biochemistry, 35(5), 1831-1845.
Liu, L., Zong, C., Li, B., Shen, D., Tang, Z., Chen, J., Zheng, Q., Tong, X., Gao, C., &
Wang, J. (2014). The interaction between 1 integrins and ERK1/2 in osteogenic
differentiation of human mesenchymal stem cells under fluid shear stress modelled
by a perfusion system. Journal of Tissue Engineering and Regenerative Medicine,
8(2), 85-96.
Lui, P. (2015). Stem cell technology for tendon regeneration: current status, challenges,
and future research directions. Stem Cells and Cloning: Advances and Applications,
Volume 8, 163-174.
Mackey, A. L., Heinemeier, K. M., Koskinen, S. O., & Kjaer, M. (2008). Dynamic
adaptation of tendon and muscle connective tissue to mechanical loading.
Connective Tissue Research, 49(3), 165-168.
Maffulli, N., Sharma, P., & Luscombe, K. L. (2004). Achilles tendinopathy: aetiology and
management. Journal of the Royal Society of Medicine, 97(10), 472-476.
Maffulli, N., Wong, J., & Almekinders, L. C. (2003). Types and epidemiology of
tendinopathy. Clinics in Sports Medicine, 22(4), 675-692.
Maniotis, A. J., Chen, C. S., & Ingber, D. E. (1997). Demonstration of mechanical
connections between integrins, cytoskeletal filaments, and nucleoplasm that
stabilize nuclear structure. Proceedings of the National Academy of Sciences of the
United States of America, 94(3), 849-854.
Mao, X., Gavara, N., & Song, G. (2015). Nuclear Mechanics and Stem Cell
Differentiation. Stem Cell Reviews and Reports, 11(6), 804-812.
McBeath, R., Pirone, D. M., Nelson, C. M., Bhadriraju, K., & Chen, C. S. (2004). Cellshape, cytoskeletal tension, and RhoA regulate stem cell lineage commitment.
Developmental Cell, 6(4), 483-495.
McNeilly, C. M., Banes, A. J., Benjamin, M., & Ralphs, J. R. (1996). Tendon cells in vivo
form a three dimensional network of cell processes linked by gap junctions. Journal
of Anatomy, 189(3), 593.
Murchison, N. D., Price, B. A., Conner, D. A., Keene, D. R., Olson, E. N., Tabin, C. J., &
Schweitzer, R. (2007). Regulation of tendon differentiation by scleraxis
distinguishes force-transmitting tendons from muscle-anchoring tendons.
Development, 134(14), 2697-2708.
Nobes, C. D., & Hall, A. (1995). Rho, rac, and cdc42 GTPases regulate the assembly of
multimolecular focal complexes associated with actin stress fibers, lamellipodia,
and filopodia. Cell, 81(1), 53-62.
Pankov, R., Cukierman, E., Katz, B.Z., Matsumoto, K., Lin, D. C., Lin, S., Hahn, C., &
Yamada, K. M. (2000). Integrin dynamics and matrix assembly tensin-dependent
translocation of α5β1 integrins promotes early fibronectin fibrillogenesis. The
Journal of Cell Biology, 148(5), 1075-1090.
Parker, K. K., Tan, J., Chen, C. S., & Tung, L. (2008). Myofibrillar architecture in
engineered cardiac myocytes. Circulation Research. 103(4), 340-2
Popov, C., Burggraf, M., Kreja, L., Ignatius, A., Schieker, M., & Docheva, D. (2015).
Mechanical stimulation of human tendon stem/progenitor cells results in
upregulation of matrix proteins, integrins and MMPs, and activation of p38 and
ERK1/2 kinases. BMC Molecular Biology, 16(1), 1-11.
Puckelwartz, M. J., Kessler, E. J., Kim, G., Dewitt, M. M., Zhang, Y., Earley, J. U.,
Depreux, F. F., Holaska, J., Mewborn, S. K., Pytel, P., & McNally, E. M. (2010).
Nesprin-1 mutations in human and murine cardiomyopathy. Journal of Molecularand Cellular Cardiology, 48(4), 600-608.
Rajgor, D., & Shanahan, C. M. (2013). Nesprins: from the nuclear envelope and beyond.
Expert Reviews in Molecular Medicine, 15, e5
Rodríguez, P. J., González, M., Ríos, S., & Cambiazo, V. (2004). Cytoskeletal organization
of human mesenchymal stem cells (MSC) changes during their osteogenic
differentiation. Journal of Cellular Biochemistry, 93(4), 721-731.
Ruiz, S., & Chen, C. S. (2006). Microcontact printing: A tool to pattern. Soft Matter, 168-
177.
Schwartz, M. A., & Ginsberg, M. H. (2002). Networks and crosstalk: integrin signalling
spreads. Nature Cell Biology, 4(4).
Scott, A., Huisman, E., & Khan, K. (2011). Conservative treatment of chronic Achilles
tendinopathy. Canadian Medical Association Journal, 183(10), 1159-1165.
Sharma, P., & Maffulli, N. (1997). Biology of tendon injury: healing, modeling and
remodeling. Jounal of Musculoskelet Neuronal Interaction, 6(2), 181-190.
Shih, Y.R. V., Tseng, K.F., Lai, H.Y., Lin, C.H., & Lee, O. K. (2011). Matrix stiffness
regulation of integrin-mediated mechanotransduction during osteogenic
differentiation of human mesenchymal stem cells. Journal of Bone and Mineral
Research, 26(4), 730-738.
Shukunami, C., Takimoto, A., Oro, M., Hiraki, Y., Shukunami, C., Takimoto, A., Oro, M.,
& Hiraki, Y. (2006). Scleraxis positively regulates the expression of tenomodulin, a
differentiation marker of tenocytes. Developmental Biology.
Sordella, R., Jiang, W., Chen, G.C., Curto, M., & Settleman, J. (2003). Modulation of Rho
GTPase Signaling Regulates a Switch between Adipogenesis and Myogenesis. Cell,
113(2), 147-158.
Sosa, B. A., Rothballer, A., Kutay, U., & Schwartz, T. U. (2012). LINC complexes form bybinding of three KASH peptides to domain interfaces of trimeric SUN proteins.
Cell, 149(5), 1035-1047.
Spatz, J. P., & Geiger, B. (2007). Molecular engineering of cellular environments: cell
adhesion to nano-digital surfaces. Methods in Cell biology, 83, 89-111.
Takano, H., Komuro, I., Oka, T., Shiojima, I., Hiroi, Y., Mizuno, T., & Yazaki, Y. (1998).
The Rho Family G Proteins Play a Critical Role in Muscle Differentiation.
Molicular Cell Biology, 18(3), 1580-1589.
Taranum, S., Sur, I., Müller, R., Lu, W., Rashmi, R. N., Munck, M., Neumann, S.,
Karakesisoglou, I., & Noegel, A. A. (2012). Cytoskeletal Interactions at the Nuclear
Envelope Mediated by Nesprins. International Journal of Cell Biology, 2012,
736524.
Tay, C., Yu, H., Pal, M., Leong, W., Tan, N., Ng, K., Leong, D., & Tan, L. (2010).
Micropatterned matrix directs differentiation of human mesenchymal stem cells
towards myocardial lineage. Experimental Cell Research, 316(7), 1159-1168.
Théry, M. (2010). Micropatterning as a tool to decipher cell morphogenesis and functions.
Journal of Cell Science, 123(24), 4201-4213.
Théry, M., Pépin, A., Dressaire, E., Chen, Y., & Bornens, M. (2006). Cell distribution of
stress fibres in response to the geometry of the adhesive environment. Cell Motility
and the Cytoskeleton, 63(6), 341-355.
Via, A., Papa, G., Oliva, F., & Maffulli, N. (2016). Tendinopathy. Current Physical
Medicine and Rehabilitation Reports, 4(1), 50-55.
Voleti, P. B., Buckley, M. R., & Soslowsky, L. J. (2012). Tendon Healing: Repair and
Regeneration. Annual Review of Biomedical Engineering, 14(1), 47-71.
Wang, H., Rusielewicz, T., Tewari, A., Leitman, E. M., Einheber, S., & Melendez-Vasquez,
C. V. (2012). Myosin II is a negative regulator of oligodendrocyte morphologicaldifferentiation. Journal of Neuroscience Research, 90(8), 1547-1550
Wang, W., Li, J., Wang, K., Zhang, Z., Zhang, W., Zhou, G., Cao, Y., Ye, M., Zou, H., &
Liu, W. (2015). Induction of predominant tenogenic phenotype in human dermal
fibroblasts via synergistic effect of TGF-β and elongated cell shape. American
journal of physiology. Cell Physiology, 310(5), C357-72
Wang, Y. K., Yu, X., Cohen, D. M., Wozniak, M. A., Yang, M. T., Gao, L., Eyckmans, J., &
Chen, C. S. (2012). Bone morphogenetic protein-2-induced signaling and
osteogenesis is regulated by cell shape, RhoA/ROCK, and cytoskeletal tension.
Stem Cells and Development, 21(7), 1176-1186.
Wilhelmsen, K., Litjens, S. H. M., & Kuikman, I. (2005). Nesprin-3, a novel outer nuclear
membrane protein, associates with the cytoskeletal linker protein plectin. The
Journal of Cell Biology 171 (5), 799-810
Xu, B., Song, G., Ju, Y., Li, X., Song, Y., & Watanabe, S. (2012). RhoA/ROCK,
cytoskeletal dynamics, and focal adhesion kinase are required for mechanical
stretch-induced tenogenic differentiation of human mesenchymal stem cells.
Journal of Cellular Physiology, 227(6), 2722-2729.
Yang, Y., Relan, N. K., Przywara, D. A., & Schuger, L. (1999). Embryonic mesenchymal
cells share the potential for smooth muscle differentiation: myogenesis is controlled
by the cell's shape. Development 126(13), 3027-33.
Yim, E., Darling, E. M., Kulangara, K., Guilak, F., & Leong, K. W. (2010).
Nanotopography-induced changes in focal adhesions, cytoskeletal organization, and
mechanical properties of human mesenchymal stem cells. Biomaterials, 31(6),
1299-1306.
Yin, Z., Chen, X., Chen, J. L., Shen, W. L., Hieu Nguyen, T. M., Gao, L., & Ouyang, H. W.
(2010). The regulation of tendon stem cell differentiation by the alignment ofnanofibers. Biomaterials, 31(8), 2163-2175.
Zhang, C., Yuan, H., Liu, H., Chen, X., Lu, P., Zhu, T., Yang, L., Yin, Z., Heng, B., Zhang,
Y., & Ouyang, H. (2015). Well-aligned chitosan-based ultrafine fibers committed
teno-lineage differentiation of human induced pluripotent stem cells for Achilles
tendon regeneration. Biomaterials, 53, 716-730.
Zhang, D., Sun, M. B., Lee, J., Abdeen, A. A., & Kilian, K. A. (2016). Cell shape and the
presentation of adhesion ligands guide smooth muscle myogenesis. Journal of
Biomedical Materials Research Part A, 104(5), 1212-1220.
Zhang, J., & Wang, J. H. (2010). Characterization of differential properties of rabbit tendon
stem cells and tenocytes. BMC Musculoskelet Disorders, 11, 10.
Zhang, Q., Bethmann, C., Worth, N. F., Davies, J. D., Wasner, C., Feuer, A., Ragnauth, C.
D., Yi, Q., Mellad, J. A., Warren, D. T., Wheeler, M. A., Ellis, J. A., Skepper, J. N.,
Vorgerd, M., Schlotter-Weigel, B., Weissberg, P. L., Roberts, R. G., Wehnert, M., &
Shanahan, C. M. (2007). Nesprin-1 and -2 are involved in the pathogenesis of
Emery Dreifuss muscular dystrophy and are critical for nuclear envelope integrity.
Human Molecular Genetics, 16(23), 2816-2833.
Zhu, J., Li, J., Wang, B., Zhang, W. J., Zhou, G., Cao, Y., & Liu, W. (2010). The regulation
of phenotype of cultured tenocytes by microgrooved surface structure.
Biomaterials, 31(27), 6952-6958.
Zwolanek, D., Flicker, M., Kirstätter, E., Zaucke, F., van Osch, G., & Erben, R. G. (2015).
β1 Integrins Mediate Attachment of Mesenchymal Stem Cells to Cartilage Lesions.
BioResearch Open Access, 4(1), 39-53.