FREE SHIPPING over $40
OVER 9000 FIVE-STAR REVIEWS
5% OFF ALL SUBSCRIPTIONS
100% HAPPINESS GUARANTEE
Analyze Diet
0
Home / Equine Research Bank / BMC Cell Biol / Novel roles for scleraxis in regulating adult tenocyte funct...
BMC cell biology2018; 19(1); 14; doi: 10.1186/s12860-018-0166-z

Novel roles for scleraxis in regulating adult tenocyte function.

Abstract: Tendinopathies are common and difficult to resolve due to the formation of scar tissue that reduces the mechanical integrity of the tissue, leading to frequent reinjury. Tenocytes respond to both excessive loading and unloading by producing pro-inflammatory mediators, suggesting that these cells are actively involved in the development of tendon degeneration. The transcription factor scleraxis (Scx) is required for the development of force-transmitting tendon during development and for mechanically stimulated tenogenesis of stem cells, but its function in adult tenocytes is less well-defined. The aim of this study was to further define the role of Scx in mediating the adult tenocyte mechanoresponse. Equine tenocytes exposed to siRNA targeting Scx or a control siRNA were maintained under cyclic mechanical strain before being submitted for RNA-seq analysis. Focal adhesions and extracellular matrix-receptor interaction were among the top gene networks downregulated in Scx knockdown tenocytes. Correspondingly, tenocytes exposed to Scx siRNA were significantly softer, with longer vinculin-containing focal adhesions, and an impaired ability to migrate on soft surfaces. Other pathways affected by Scx knockdown included increased oxidative phosphorylation and diseases caused by endoplasmic reticular stress, pointing to a larger role for Scx in maintaining tenocyte homeostasis. Our study identifies several novel roles for Scx in adult tenocytes, which suggest that Scx facilitates mechanosensing by regulating the expression of several mechanosensitive focal adhesion proteins. Furthermore, we identified a number of other pathways and targets affected by Scx knockdown that have the potential to elucidate the role that tenocytes may play in the development of degenerative tendinopathy.
Get Full Text
Publication Date: 2018-08-07 PubMed ID: 30086712PubMed Central: PMC6081934DOI: 10.1186/s12860-018-0166-zGoogle Scholar: Lookup
The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
LinkedInCopy
  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study investigates the role of the scleraxis (Scx) protein in adult tenocytes (cells that help maintain tendon health), suggesting it facilitates their ability to sense mechanical stimuli. It also reveals that reducing Scx levels affects several other functions of tenocytes, which may illuminate how these cells contribute to degenerative tendon diseases.

Objective of the Study

  • The study aims to delve deeper into understanding the function of the scleraxis (Scx) protein in adult tenocytes, which are cells vital for maintaining tendon health. It seeks to comprehend the effect of reducing Scx levels on these cells.

Methodology of the Study

  • The researchers introduced small interfering RNA (siRNA) to equine tenocytes to reduce the levels of Scx. This method, known as Scx knockdown, aimed to observe how these reduced Scx levels would impact the tenocytes.
  • The tenocytes were then put under cyclic mechanical strain before undergoing a RNA-seq analysis. This analysis aids in examining the impact of the Scx knockdown on the genes within the tenocytes.

Findings of the Study

  • The study found that crucial gene networks, specifically the focal adhesions and extracellular matrix-receptor interactions, were significantly downregulated when Scx was knocked down.
  • Tenocytes with reduced Scx levels were found to be softer, with extended vinculin-containing focal adhesions. They also displayed an impaired ability to move on soft surfaces.
  • The Scx knockdown also elevated oxidative phosphorylation types and diseases caused by Endoplasmic Reticulum (ER) stress, suggesting Scx plays a larger role in keeping the tenocyte’s state balanced (homeostasis).

Implications of the Study

  • The study uncovers several new roles for Scx in adult tenocytes, especially in enabling these cells to sense mechanosensitive stimuli. It arrives at this conclusion by assessing the impact on various mechanosensitive focal adhesion proteins when Scx levels are reduced.
  • Moving forward, these findings could reveal other pathways and targets influenced by Scx knockdown. This could possibly elucidate the role that tenocytes play in developing degenerative tendon diseases, allowing for further advancements in the field.

Cite This Article

APA
Nichols AEC, Settlage RE, Werre SR, Dahlgren LA. (2018). Novel roles for scleraxis in regulating adult tenocyte function. BMC Cell Biol, 19(1), 14. https://doi.org/10.1186/s12860-018-0166-z

Publication

BMC cell biology
ISSN: 1471-2121
NlmUniqueID: 100966972
Country: England
Language: English
Volume: 19
Issue: 1
Pages: 14
PII: 14

Researcher Affiliations

Nichols, Anne E C
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, 205 Duck Pond Drive, Blacksburg, VA, 24061-0442, USA.
Settlage, Robert E
  • Advanced Research Computing, Virginia Biocomplexity Institute, Virginia Tech, Blacksburg, VA, 24061, USA.
Werre, Stephen R
  • Laboratory for Study Design and Statistical Analysis, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, 24061, USA.
Dahlgren, Linda A
  • Department of Large Animal Clinical Sciences, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, 205 Duck Pond Drive, Blacksburg, VA, 24061-0442, USA. lad11@vt.edu.

MeSH Terms

  • Aging / metabolism
  • Animals
  • Base Composition / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Cell Movement
  • Cell Nucleus Shape
  • Cytoskeleton / metabolism
  • Down-Regulation / genetics
  • Focal Adhesions / metabolism
  • Gene Expression Profiling
  • Gene Knockdown Techniques
  • Gene Ontology
  • Horses
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Small Interfering / metabolism
  • Reproducibility of Results
  • Sequence Analysis, RNA
  • Tendons / cytology
  • Tenocytes / metabolism

Conflict of Interest Statement

ETHICS APPROVAL AND CONSENT TO PARTICIPATE: Collection of equine tissues for cell isolation was approved by the Virginia Tech IACUC under protocols 14–128 and 15–059. CONSENT FOR PUBLICATION: Not applicable COMPETING INTERESTS: The authors declare that they have no competing interests. PUBLISHER’S NOTE: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

References

This article includes 60 references
  1. Yelin E, Weinstein S, King T. The burden of musculoskeletal diseases in the United States.. Semin Arthritis Rheum 2016 Dec;46(3):259-260.
    doi: 10.1016/j.semarthrit.2016.07.013pubmed: 27519477google scholar: lookup
  2. Clegg PD. Musculoskeletal disease and injury, now and in the future. Part 2: Tendon and ligament injuries.. Equine Vet J 2012 May;44(3):371-5.
    doi: 10.1111/j.2042-3306.2012.00563.xpubmed: 22486548google scholar: lookup
  3. Yang G, Rothrauff BB, Tuan RS. Tendon and ligament regeneration and repair: clinical relevance and developmental paradigm.. Birth Defects Res C Embryo Today 2013 Sep;99(3):203-222.
    doi: 10.1002/bdrc.21041pmc: PMC4041869pubmed: 24078497google scholar: lookup
  4. Goldin M, Malanga GA. Tendinopathy: a review of the pathophysiology and evidence for treatment.. Phys Sportsmed 2013 Sep;41(3):36-49.
    doi: 10.3810/psm.2013.09.2019pubmed: 24113701google scholar: lookup
  5. Birch HL. Tendon matrix composition and turnover in relation to functional requirements.. Int J Exp Pathol 2007 Aug;88(4):241-8.
    doi: 10.1111/j.1365-2613.2007.00552.xpmc: PMC2517317pubmed: 17696905google scholar: lookup
  6. Xu Y, Murrell GA. The basic science of tendinopathy.. Clin Orthop Relat Res 2008 Jul;466(7):1528-38.
    doi: 10.1007/s11999-008-0286-4pmc: PMC2505234pubmed: 18478310google scholar: lookup
  7. Gardner K, Arnoczky SP, Caballero O, Lavagnino M. The effect of stress-deprivation and cyclic loading on the TIMP/MMP ratio in tendon cells: an in vitro experimental study.. Disabil Rehabil 2008;30(20-22):1523-9.
    doi: 10.1080/09638280701785395pubmed: 18665569google scholar: lookup
  8. Schweitzer R, Chyung JH, Murtaugh LC, Brent AE, Rosen V, Olson EN, Lassar A, Tabin CJ. Analysis of the tendon cell fate using Scleraxis, a specific marker for tendons and ligaments.. Development 2001 Oct;128(19):3855-66.
    pubmed: 11585810doi: 10.1242/dev.128.19.3855google scholar: lookup
  9. Murchison ND, Price BA, Conner DA, Keene DR, Olson EN, Tabin CJ, Schweitzer R. Regulation of tendon differentiation by scleraxis distinguishes force-transmitting tendons from muscle-anchoring tendons.. Development 2007 Jul;134(14):2697-708.
    doi: 10.1242/dev.001933pubmed: 17567668google scholar: lookup
  10. Bavin EP, Atkinson F, Barsby T, Guest DJ. Scleraxis Is Essential for Tendon Differentiation by Equine Embryonic Stem Cells and in Equine Fetal Tenocytes.. Stem Cells Dev 2017 Mar 15;26(6):441-450.
    doi: 10.1089/scd.2016.0279pubmed: 27899062google scholar: lookup
  11. 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 Jun;11(2):124-32.
    pubmed: 21625049
  12. Kuo CK, Tuan RS. Mechanoactive tenogenic differentiation of human mesenchymal stem cells.. Tissue Eng Part A 2008 Oct;14(10):1615-27.
    doi: 10.1089/ten.tea.2006.0415pubmed: 18759661google scholar: lookup
  13. Li Y, Ramcharan M, Zhou Z, Leong DJ, Akinbiyi T, Majeska RJ, Sun HB. The Role of Scleraxis in Fate Determination of Mesenchymal Stem Cells for Tenocyte Differentiation.. Sci Rep 2015 Aug 20;5:13149.
    doi: 10.1038/srep13149pmc: PMC4542341pubmed: 26289033google scholar: lookup
  14. 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 Jun 7;21(11):933-41.
    doi: 10.1016/j.cub.2011.04.007pmc: PMC3118584pubmed: 21600772google scholar: lookup
  15. Mendias CL, Gumucio JP, Bakhurin KI, Lynch EB, Brooks SV. Physiological loading of tendons induces scleraxis expression in epitenon fibroblasts.. J Orthop Res 2012 Apr;30(4):606-12.
    doi: 10.1002/jor.21550pmc: PMC3245815pubmed: 21913219google scholar: lookup
  16. Andrews S. FastQC: a quality control tool for high throughput sequence data. .
  17. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data.. Bioinformatics 2014 Aug 1;30(15):2114-20.
    doi: 10.1093/bioinformatics/btu170pmc: PMC4103590pubmed: 24695404google scholar: lookup
  18. Kim D, Langmead B, Salzberg SL. HISAT: a fast spliced aligner with low memory requirements.. Nat Methods 2015 Apr;12(4):357-60.
    doi: 10.1038/nmeth.3317pmc: PMC4655817pubmed: 25751142google scholar: lookup
  19. Anders S, Pyl PT, Huber W. HTSeq--a Python framework to work with high-throughput sequencing data.. Bioinformatics 2015 Jan 15;31(2):166-9.
    doi: 10.1093/bioinformatics/btu638pmc: PMC4287950pubmed: 25260700google scholar: lookup
  20. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2.. Genome Biol 2014;15(12):550.
    doi: 10.1186/s13059-014-0550-8pmc: PMC4302049pubmed: 25516281google scholar: lookup
  21. 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 Dec;25(4):402-8.
    doi: 10.1006/meth.2001.1262pubmed: 11846609google scholar: lookup
  22. Cardwell RD, Dahlgren LA, Goldstein AS. Electrospun fibre diameter, not alignment, affects mesenchymal stem cell differentiation into the tendon/ligament lineage.. J Tissue Eng Regen Med 2014 Dec;8(12):937-45.
    doi: 10.1002/term.1589pubmed: 23038413google scholar: lookup
  23. Ford AJ, Jain G, Rajagopalan P. Designing a fibrotic microenvironment to investigate changes in human liver sinusoidal endothelial cell function.. Acta Biomater 2015 Sep;24:220-7.
    doi: 10.1016/j.actbio.2015.06.028pubmed: 26117313google scholar: lookup
  24. Thomas G, Burnham NA, Camesano TA, Wen Q. Measuring the mechanical properties of living cells using atomic force microscopy.. J Vis Exp 2013 Jun 27;(76).
    pmc: PMC3729185pubmed: 23851674doi: 10.3791/50497google scholar: lookup
  25. Jelinsky SA, Archambault J, Li L, Seeherman H. Tendon-selective genes identified from rat and human musculoskeletal tissues.. J Orthop Res 2010 Mar;28(3):289-97.
    pubmed: 19780194doi: 10.1002/jor.20999google scholar: lookup
  26. Dyment NA, Liu CF, Kazemi N, Aschbacher-Smith LE, Kenter K, Breidenbach AP, Shearn JT, Wylie C, Rowe DW, Butler DL. The paratenon contributes to scleraxis-expressing cells during patellar tendon healing.. PLoS One 2013;8(3):e59944.
    doi: 10.1371/journal.pone.0059944pmc: PMC3608582pubmed: 23555841google scholar: lookup
  27. Scott A, Sampaio A, Abraham T, Duronio C, Underhill TM. Scleraxis expression is coordinately regulated in a murine model of patellar tendon injury.. J Orthop Res 2011 Feb;29(2):289-96.
    doi: 10.1002/jor.21220pmc: PMC3951487pubmed: 20740671google scholar: lookup
  28. Muir T, Sadler-Riggleman I, Skinner MK. Role of the basic helix-loop-helix transcription factor, scleraxis, in the regulation of Sertoli cell function and differentiation.. Mol Endocrinol 2005 Aug;19(8):2164-74.
    doi: 10.1210/me.2004-0473pubmed: 15831523google scholar: lookup
  29. Levay AK, Peacock JD, Lu Y, Koch M, Hinton RB Jr, Kadler KE, Lincoln J. Scleraxis is required for cell lineage differentiation and extracellular matrix remodeling during murine heart valve formation in vivo.. Circ Res 2008 Oct 24;103(9):948-56.
    doi: 10.1161/CIRCRESAHA.108.177238pmc: PMC2743952pubmed: 18802027google scholar: lookup
  30. Taylor SE, Vaughan-Thomas A, Clements DN, Pinchbeck G, Macrory LC, Smith RK, Clegg PD. Gene expression markers of tendon fibroblasts in normal and diseased tissue compared to monolayer and three dimensional culture systems.. BMC Musculoskelet Disord 2009 Feb 26;10:27.
    doi: 10.1186/1471-2474-10-27pmc: PMC2651848pubmed: 19245707google scholar: lookup
  31. Watts AE, Nixon AJ, Yeager AE, Mohammed HO. A collagenase gel/physical defect model for controlled induction of superficial digital flexor tendonitis.. Equine Vet J 2012 Sep;44(5):576-86.
    doi: 10.1111/j.2042-3306.2011.00471.xpubmed: 21950378google scholar: lookup
  32. Benjamini Y, Speed TP. Summarizing and correcting the GC content bias in high-throughput sequencing.. Nucleic Acids Res 2012 May;40(10):e72.
    doi: 10.1093/nar/gks001pmc: PMC3378858pubmed: 22323520google scholar: lookup
  33. Risso D, Schwartz K, Sherlock G, Dudoit S. GC-content normalization for RNA-Seq data.. BMC Bioinformatics 2011 Dec 17;12:480.
    doi: 10.1186/1471-2105-12-480pmc: PMC3315510pubmed: 22177264google scholar: lookup
  34. Love MI, Hogenesch JB, Irizarry RA. Modeling of RNA-seq fragment sequence bias reduces systematic errors in transcript abundance estimation.. Nat Biotechnol 2016 Dec;34(12):1287-1291.
    doi: 10.1038/nbt.3682pmc: PMC5143225pubmed: 27669167google scholar: lookup
  35. Ross TD, Coon BG, Yun S, Baeyens N, Tanaka K, Ouyang M, Schwartz MA. Integrins in mechanotransduction.. Curr Opin Cell Biol 2013 Oct;25(5):613-8.
    doi: 10.1016/j.ceb.2013.05.006pmc: PMC3757118pubmed: 23797029google scholar: lookup
  36. Campbell ID, Humphries MJ. Integrin structure, activation, and interactions.. Cold Spring Harb Perspect Biol 2011 Mar 1;3(3).
    pmc: PMC3039929pubmed: 21421922doi: 10.1101/cshperspect.a004994google scholar: lookup
  37. Patil S, Jedsadayanmata A, Wencel-Drake JD, Wang W, Knezevic I, Lam SC. Identification of a talin-binding site in the integrin beta(3) subunit distinct from the NPLY regulatory motif of post-ligand binding functions. The talin n-terminal head domain interacts with the membrane-proximal region of the beta(3) cytoplasmic tail.. J Biol Chem 1999 Oct 1;274(40):28575-83.
    doi: 10.1074/jbc.274.40.28575pubmed: 10497223google scholar: lookup
  38. Yan J, Yao M, Goult BT, Sheetz MP. Talin Dependent Mechanosensitivity of Cell Focal Adhesions.. Cell Mol Bioeng 2015;8(1):151-159.
    doi: 10.1007/s12195-014-0364-5pmc: PMC4468797pubmed: 26097520google scholar: lookup
  39. Rahikainen R, von Essen M, Schaefer M, Qi L, Azizi L, Kelly C, Ihalainen TO, Wehrle-Haller B, Bastmeyer M, Huang C, Hytönen VP. Mechanical stability of talin rod controls cell migration and substrate sensing.. Sci Rep 2017 Jun 15;7(1):3571.
    doi: 10.1038/s41598-017-03335-2pmc: PMC5472591pubmed: 28620171google scholar: lookup
  40. Austen K, Ringer P, Mehlich A, Chrostek-Grashoff A, Kluger C, Klingner C, Sabass B, Zent R, Rief M, Grashoff C. Extracellular rigidity sensing by talin isoform-specific mechanical linkages.. Nat Cell Biol 2015 Dec;17(12):1597-606.
    doi: 10.1038/ncb3268pmc: PMC4662888pubmed: 26523364google scholar: lookup
  41. Humphries JD, Wang P, Streuli C, Geiger B, Humphries MJ, Ballestrem C. Vinculin controls focal adhesion formation by direct interactions with talin and actin.. J Cell Biol 2007 Dec 3;179(5):1043-57.
    doi: 10.1083/jcb.200703036pmc: PMC2099183pubmed: 18056416google scholar: lookup
  42. Saunders RM, Holt MR, Jennings L, Sutton DH, Barsukov IL, Bobkov A, Liddington RC, Adamson EA, Dunn GA, Critchley DR. Role of vinculin in regulating focal adhesion turnover.. Eur J Cell Biol 2006 Jun;85(6):487-500.
    doi: 10.1016/j.ejcb.2006.01.014pubmed: 16584805google scholar: lookup
  43. Cunningham-Edmondson AC, Hanks SK. p130Cas substrate domain signaling promotes migration, invasion, and survival of estrogen receptor-negative breast cancer cells.. Breast Cancer (Dove Med Press) 2009;1:39-52.
    pmc: PMC3022348pubmed: 24367162doi: 10.2147/bctt.s6255google scholar: lookup
  44. Honda H, Nakamoto T, Sakai R, Hirai H. p130(Cas), an assembling molecule of actin filaments, promotes cell movement, cell migration, and cell spreading in fibroblasts.. Biochem Biophys Res Commun 1999 Aug 19;262(1):25-30.
    doi: 10.1006/bbrc.1999.1162pubmed: 10448062google scholar: lookup
  45. Ortensi B, Osti D, Pellegatta S, Pisati F, Brescia P, Fornasari L, Levi D, Gaetani P, Colombo P, Ferri A, Nicolis S, Finocchiaro G, Pelicci G. Rai is a new regulator of neural progenitor migration and glioblastoma invasion.. Stem Cells 2012 May;30(5):817-32.
    doi: 10.1002/stem.1056pubmed: 22311806google scholar: lookup
  46. Fagiani E, Giardina G, Luzi L, Cesaroni M, Quarto M, Capra M, Germano G, Bono M, Capillo M, Pelicci P, Lanfrancone L. RaLP, a new member of the Src homology and collagen family, regulates cell migration and tumor growth of metastatic melanomas.. Cancer Res 2007 Apr 1;67(7):3064-73.
    doi: 10.1158/0008-5472.CAN-06-2301pubmed: 17409413google scholar: lookup
  47. Peyton SR, Ghajar CM, Khatiwala CB, Putnam AJ. The emergence of ECM mechanics and cytoskeletal tension as important regulators of cell function.. Cell Biochem Biophys 2007;47(2):300-20.
    doi: 10.1007/s12013-007-0004-ypubmed: 17652777google scholar: lookup
  48. Solon J, Levental I, Sengupta K, Georges PC, Janmey PA. Fibroblast adaptation and stiffness matching to soft elastic substrates.. Biophys J 2007 Dec 15;93(12):4453-61.
    doi: 10.1529/biophysj.106.101386pmc: PMC2098710pubmed: 18045965google scholar: lookup
  49. Arnoczky SP, Lavagnino M, Egerbacher M, Caballero O, Gardner K, Shender MA. Loss of homeostatic strain alters mechanostat "set point" of tendon cells in vitro.. Clin Orthop Relat Res 2008 Jul;466(7):1583-91.
    doi: 10.1007/s11999-008-0264-xpmc: PMC2505257pubmed: 18459031google scholar: lookup
  50. Lavagnino M, Arnoczky SP. In vitro alterations in cytoskeletal tensional homeostasis control gene expression in tendon cells.. J Orthop Res 2005 Sep;23(5):1211-8.
    doi: 10.1016/j.orthres.2005.04.001pubmed: 15908162google scholar: lookup
  51. Gardner K, Lavagnino M, Egerbacher M, Arnoczky SP. Re-establishment of cytoskeletal tensional homeostasis in lax tendons occurs through an actin-mediated cellular contraction of the extracellular matrix.. J Orthop Res 2012 Nov;30(11):1695-701.
    doi: 10.1002/jor.22131pubmed: 22517354google scholar: lookup
  52. Xu W, Mezencev R, Kim B, Wang L, McDonald J, Sulchek T. Cell stiffness is a biomarker of the metastatic potential of ovarian cancer cells.. PLoS One 2012;7(10):e46609.
    doi: 10.1371/journal.pone.0046609pmc: PMC3464294pubmed: 23056368google scholar: lookup
  53. Beliveau A, Thomas G, Gong J, Wen Q, Jain A. Aligned Nanotopography Promotes a Migratory State in Glioblastoma Multiforme Tumor Cells.. Sci Rep 2016 May 18;6:26143.
    doi: 10.1038/srep26143pmc: PMC4870554pubmed: 27189099google scholar: lookup
  54. Kole TP, Tseng Y, Jiang I, Katz JL, Wirtz D. Intracellular mechanics of migrating fibroblasts.. Mol Biol Cell 2005 Jan;16(1):328-38.
    doi: 10.1091/mbc.e04-06-0485pmc: PMC539176pubmed: 15483053google scholar: lookup
  55. Lee JS, Hale CM, Panorchan P, Khatau SB, George JP, Tseng Y, Stewart CL, Hodzic D, Wirtz D. Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration.. Biophys J 2007 Oct 1;93(7):2542-52.
    doi: 10.1529/biophysj.106.102426pmc: PMC1965451pubmed: 17631533google scholar: lookup
  56. Deng S, Huang C. E3 ubiquitin ligases in regulating stress fiber, lamellipodium, and focal adhesion dynamics.. Cell Adh Migr 2014;8(1):49-54.
    doi: 10.4161/cam.27480pmc: PMC3974793pubmed: 24589622google scholar: lookup
  57. Bravo R, Parra V, Gatica D, Rodriguez AE, Torrealba N, Paredes F, Wang ZV, Zorzano A, Hill JA, Jaimovich E, Quest AF, Lavandero S. Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration.. Int Rev Cell Mol Biol 2013;301:215-90.
    doi: 10.1016/B978-0-12-407704-1.00005-1pmc: PMC3666557pubmed: 23317820google scholar: lookup
  58. Groenendyk J, Lee D, Jung J, Dyck JR, Lopaschuk GD, Agellon LB, Michalak M. Inhibition of the Unfolded Protein Response Mechanism Prevents Cardiac Fibrosis.. PLoS One 2016;11(7):e0159682.
    doi: 10.1371/journal.pone.0159682pmc: PMC4956237pubmed: 27441395google scholar: lookup
  59. Marcinak SJ, Ron D. The unfolded protein response in lung disease.. Proc Am Thorac Soc 2010 Nov;7(6):356-62.
    doi: 10.1513/pats.201001-015AWpmc: PMC3136955pubmed: 21030513google scholar: lookup
  60. Malhi H, Kaufman RJ. Endoplasmic reticulum stress in liver disease.. J Hepatol 2011 Apr;54(4):795-809.
    doi: 10.1016/j.jhep.2010.11.005pmc: PMC3375108pubmed: 21145844google scholar: lookup

Citations

This article has been cited 19 times.
  1. Maffulli N, Cuozzo F, Migliorini F, Oliva F. The tendon unit: biochemical, biomechanical, hormonal influences.. J Orthop Surg Res 2023 Apr 21;18(1):311.
    doi: 10.1186/s13018-023-03796-4pubmed: 37085854google scholar: lookup
  2. Chen R, Skutella T. Tendon-Specific Activation of Tenogenic Transcription Factors Enables Keeping Tenocytes' Identity In Vitro.. Int J Mol Sci 2022 Nov 15;23(22).
    doi: 10.3390/ijms232214078pubmed: 36430562google scholar: lookup
  3. Kayiran O, Tunc S, Ozcan GGE, Kaya N, Karabulut D. Tamoxifen Prevents Peritendinous Adhesions: A Preliminary Report.. Biomed Res Int 2022;2022:4250771.
    doi: 10.1155/2022/4250771pubmed: 36177054google scholar: lookup
  4. Koch DW, Schnabel LV, Ellis IM, Bates RE, Berglund AK. TGF-β2 enhances expression of equine bone marrow-derived mesenchymal stem cell paracrine factors with known associations to tendon healing.. Stem Cell Res Ther 2022 Sep 16;13(1):477.
    doi: 10.1186/s13287-022-03172-9pubmed: 36114555google scholar: lookup
  5. Shojaee A, Ejeian F, Parham A, Nasr Esfahani MH. Optimizing Tenogenic Differentiation of Equine Adipose-Derived Mesenchymal Stem Cells (eq-ASC) Using TGFB3 Along with BMP Antagonists.. Cell J 2022 Jul 27;24(7):370-379.
    doi: 10.22074/cellj.2022.7892pubmed: 36043405google scholar: lookup
  6. Jin J, Yang QQ, Zhou YL. Non-Viral Delivery of Gene Therapy to the Tendon.. Polymers (Basel) 2022 Aug 16;14(16).
    doi: 10.3390/polym14163338pubmed: 36015594google scholar: lookup
  7. Huang BZ, Jing-Jing Y, Dong XM, Zhuan Zhong, Xiao-Ning Liu. Analysis of the lncRNA-Associated Competing Endogenous RNA (ceRNA) Network for Tendinopathy.. Genet Res (Camb) 2022;2022:9792913.
    doi: 10.1155/2022/9792913pubmed: 35645614google scholar: lookup
  8. Ciardulli MC, Lovecchio J, Scala P, Lamparelli EP, Dale TP, Giudice V, Giordano E, Selleri C, Forsyth NR, Maffulli N, Della Porta G. 3D Biomimetic Scaffold for Growth Factor Controlled Delivery: An In-Vitro Study of Tenogenic Events on Wharton's Jelly Mesenchymal Stem Cells.. Pharmaceutics 2021 Sep 10;13(9).
    doi: 10.3390/pharmaceutics13091448pubmed: 34575523google scholar: lookup
  9. Nichols AEC, Muscat SN, Miller SE, Green LJ, Richards MS, Loiselle AE. Impact of isolation method on cellular activation and presence of specific tendon cell subpopulations during in vitro culture.. FASEB J 2021 Jul;35(7):e21733.
    doi: 10.1096/fj.202100405Rpubmed: 34160846google scholar: lookup
  10. Ahn KH, Park ES, Choi CY, Cha HG, Hwang Y, Nam SM. Hyaluronic Acid Treatment Improves Healing of the Tenorrhaphy Site by Suppressing Adhesions through Extracellular Matrix Remodeling in a Rat Model.. Polymers (Basel) 2021 Mar 17;13(6).
    doi: 10.3390/polym13060928pubmed: 33802991google scholar: lookup
  11. Ackerman JE, Best KT, Muscat SN, Loiselle AE. Metabolic Regulation of Tendon Inflammation and Healing Following Injury.. Curr Rheumatol Rep 2021 Feb 10;23(3):15.
    doi: 10.1007/s11926-021-00981-4pubmed: 33569739google scholar: lookup
  12. Best KT, Korcari A, Mora KE, Nichols AE, Muscat SN, Knapp E, Buckley MR, Loiselle AE. Scleraxis-lineage cell depletion improves tendon healing and disrupts adult tendon homeostasis.. Elife 2021 Jan 22;10.
    doi: 10.7554/eLife.62203pubmed: 33480357google scholar: lookup
  13. Silva DFD, de Oliveira Fujii L, Chiarotto GB, de Oliveira CA, de Andrade TAM, de Oliveira ALR, Esquisatto MAM, Mendonça FAS, Dos Santos GMT, de Aro AA. Influence of microcurrent on the modulation of remodelling genes in a wound healing assay.. Mol Biol Rep 2021 Feb;48(2):1233-1241.
    doi: 10.1007/s11033-021-06135-0pubmed: 33475929google scholar: lookup
  14. Chen ZY, Chen SH, Chen CH, Chou PY, Yang CC, Lin FH. Polysaccharide Extracted from Bletilla striata Promotes Proliferation and Migration of Human Tenocytes.. Polymers (Basel) 2020 Nov 1;12(11).
    doi: 10.3390/polym12112567pubmed: 33139654google scholar: lookup
  15. Citeroni MR, Ciardulli MC, Russo V, Della Porta G, Mauro A, El Khatib M, Di Mattia M, Galesso D, Barbera C, Forsyth NR, Maffulli N, Barboni B. In Vitro Innovation of Tendon Tissue Engineering Strategies.. Int J Mol Sci 2020 Sep 14;21(18).
    doi: 10.3390/ijms21186726pubmed: 32937830google scholar: lookup
  16. van Vijven M, Wunderli SL, Ito K, Snedeker JG, Foolen J. Serum deprivation limits loss and promotes recovery of tenogenic phenotype in tendon cell culture systems.. J Orthop Res 2021 Jul;39(7):1561-1571.
    doi: 10.1002/jor.24761pubmed: 32478872google scholar: lookup
  17. Gracey E, Burssens A, Cambré I, Schett G, Lories R, McInnes IB, Asahara H, Elewaut D. Tendon and ligament mechanical loading in the pathogenesis of inflammatory arthritis.. Nat Rev Rheumatol 2020 Apr;16(4):193-207.
    doi: 10.1038/s41584-019-0364-xpubmed: 32080619google scholar: lookup
  18. Yang F, Zhang A, Richardson DW. Regulation of the tenogenic gene expression in equine tenocyte-derived induced pluripotent stem cells by mechanical loading and Mohawk.. Stem Cell Res 2019 Aug;39:101489.
    doi: 10.1016/j.scr.2019.101489pubmed: 31277043google scholar: lookup
  19. Shojaee A, Parham A. Strategies of tenogenic differentiation of equine stem cells for tendon repair: current status and challenges.. Stem Cell Res Ther 2019 Jun 18;10(1):181.
    doi: 10.1186/s13287-019-1291-0pubmed: 31215490google scholar: lookup
Subscribe to our newsletter
Join 99,344 horse owners like you who receive our email updates on horse health and nutrition.