Modern concepts about genetic regulation of connective tissue gystophysiology and its relationship to the physical quality of "flexibility”

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"Flexibility” is a physical quality of a person, which is characterized by the ability to perform movements with a large amplitude. Flexibility is important for success in such activities as sports (artistic and rhythmic gymnastics, figure skating, etc.), as well in classical choreography, for example, ballet. Extracellular matrix producing cells and structural proteins of connective tissues take an active part in the formation of mobility of the elements of the musculoskeletal system. Connective tissues are a complex structural and functional system, the components of which are encoded by many genes. Mutations in them lead to various hereditary diseases that increase or decrease "flexibility”. The role of genes in the formation of conditions encoded in the ICD-11 LD28.Z remains unclear - "Syndromes involving connective tissue as the main feature, unspecified”, and their prognostic significance for people experiencing intense physical exertion. The purpose of this review is to generalize modern ideas about the role of genes, extracellular matrix and cells producing it in the formation of such a physical quality as flexibility.

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About the authors

A. V Zholinsky

Federal Scientific and Clinical Center for Sports Medicine and Rehabilitation FMBA of Russia

Moscow, Russia

A. I Kadykova

Federal Scientific and Clinical Center for Sports Medicine and Rehabilitation FMBA of Russia

Moscow, Russia

R. V Deev

Federal Scientific and Clinical Center for Sports Medicine and Rehabilitation FMBA of Russia; I.I. Mechnikov North-West State Medical University

Moscow, Russia; Saint Petersburg, Russia


  1. Москаленко Е.А., Ходыкина В.В. Общая характеристика гибкости как физического качества и факторы, влияющие на развитие гибкости. Обучение и воспитание: методики и практика. 2014; 11: 125-28.
  2. Германов Г.Н. Основы биомеханики: двигательные способности и физические качества (разделы теории физической культуры): учебное пособие для СПО. 2-е издание. Москва: издательство «Юрайт»; 2019. с. 13-25.
  3. Зациорский В.М. Физические качества спортсмена: основы теории и методики воспитания. 5-е издание. Москва: издательство «Спорт»; 2020. с. 157-60.
  4. Матвеев Л.П. Теория и методика физической культуры (введение теорию физической культуры; общая теория и методика физического воспитания): учебник для высших учебных заведений физкультурного профиля. 4-е издание. Москва: издательство «Спорт»; 2021. с. 364-91
  5. Behm D.G. The Science and Physiology of Flexibility and Stretching: Implications and Applications in Sport Performance and Health. 1st edition. New York: Routledge, 2019. p. 14-47.
  6. Sarbacher C. A., Halper, J.T. Connective Tissue and Age-Related Diseases. Biochemistry and Cell Biology of Ageing. Clinical Science. 2019; 2: 281-310. doi: 10.1007/978-981-13-3681-2_11.
  7. Омельяненко Н.П., Слуцкий Л.И. Соединительная ткань (гистофизиология и биохимия). Том I. Под редакцией: Миронова С.П. Москва: издательство «Известия»; 2009. с. 12-42.
  8. Hynes R.O., Naba A. Overview of the matrisome-an inventory of extracellular matrix constituents and functions. Cold Spring Harb. Perspect. Biol. 2012; 4(1): a004903. doi: 10.1101/cshperspect.a004903.
  9. Bonnans C., Chou J., Werb Z. Remodelling the extracellular matrix in development and disease. Nat. Rev. Mol. Cell Biol. 2014; 15(12):786-801. doi: 10.1038/nrm3904.
  10. Mescher L.A. Junqueira’s Basic Histology: Text and Atlas. 15 ed. McGraw-Hill Education; 2016. p. 96-120.
  11. Yi S., Ding F, Gong L., Gu X. Extracellular Matrix Scaffolds for Tissue Engineering and Regenerative Medicine. Curr. Stem Cell Res. Ther. 2017; 12(3):233-46. doi: 10.2174/1574888X11666160905092513.
  12. Martin G. R., Kleinman H.K., Terranova V.P et al. The regulation of basement membrane formation and cell-matrix interactions by defined supramolecular complexes. Ciba Foundation Symposium. 1984; 108: 197-212. doi: 10.1002/9780470720899.ch13.
  13. Naba A., Clauser K.R., Hoersch S. et al. The matrisome: in silico definition and in vivo characterization by proteomics of normal and tumor extracellular matrices. Mol. Cell Proteomics. 2012; 11(4): M111.014647. doi: 10.1074/mcp.M111.014647.
  14. Naba A., Hoersch S., Hynes R.O. Towards definition of an ECM parts list: an advance on GO categories. Matrix Biol. 2012; 31(7-8): 371-72. doi: 10.1016/j.matbio.2012.11.008.
  15. Hynes R.O., Naba A. Overview of the matrisome--an inventory of extracellular matrix constituents and functions. Cold Spring Harb. Per-spect. Biol. 2012; 4(1): a004903. doi: 10.1101/cshperspect.a004903.
  16. Matrisome project.
  17. Consortium U.P. UniProt: a hub for protein information. Nucleic Acids Res. 2015; 43(D1): D204-D212.
  18. Naba A., Clauser K.R., Ding H. et al. The extracellular matrix: Tools and insights for the “omics” era. Matrix Biol. 2016; 49:10-24. doi: 10.1016/j.matbio.2015.06.003.
  19. Online Mendelian Inheritance in Man (OMIM).
  20. Murphy-Ryan M., Psychogios A., Lindor N.M. Hereditary disorders of connective tissue: A guide to the emerging differential diagnosis. Genetics in Medicine. 2010; 12(6): 344-54. doi: 10.1097/gim.0b013e3181e074f0.
  21. Karsdal M. Biochemistry of Collagens, Laminins and Elastin Structure, Function and Biomarkers. In: Karsdal M., Leeming D.J., Henrinsen K., Bay-Jensen A-C., Nielsen S.H., Bajer C.L., editors. 2nd ed. Elsevier: Academic Press; 2019. p. 1-23.
  22. Sorushanova A., Delgado L. M., Wu Z. et al. The Collagen Suprafamily: From Biosynthesis to Advanced Biomaterial Development. 2018; 31(1): 1-39. doi: 10.1002/adma.201801651.
  23. Игнатович О.Н., Намазова-Баранова Л.С., Маргиева Т.В. и др. Несовершенный остеогенез: особенности диагностики. Педиатрическая фармакология. 2018; 15(3): 224-32. [Ignatovich O.N., Namazova-Baranova L.S., Margieva T.V. Osteogenesis imperfecta: diagnostic features. Pediatric pharmacology 2018; 15(3): 224-32.]
  24. Полякова, О. А.,. Михайлова Л. К., Садовская Ю. Е. И др. Младенческие кортикалные гиперостозы - обзор литературы и клинические случаи болезни Каффи. Кремлевская медицина. Клинический вестник. 2020; 2: 121-28.
  25. Malfait F., Francomano C., Byers P. et al. The 2017 international classification of the Ehlers-Danlos syndromes. Am. J. of Medical Genetics Part C: Seminars in Medical Genetics. 2017; 175(1): 8-26. doi: 10.1002/ajmg.c.31552.
  26. Melis D., Cappuccio G., Ginocchio V.M. et al. Cardiac valve disease: an unreported feature in Ehlers Danlos syndrome arthrocalasia type? Ital. J. Pediatr. 2012;38: 65. doi: 10.1186/1824-7288-38-65.
  27. Баранов В.С. Генетика и эпигенетика дисплазий соединительной ткани. Педиатрия. 2013; 92(4): 19-26.
  28. Wang D.D., Gao F.J., Hu F.Y. et al. Mutation Spectrum of Stickler Syndrome Type I and Genotype-phenotype Analysis in East Asian Population: a systematic review. BMC Med. Genet. 2020; 21(1): 27. doi: 10.1186/ s12881-020-0963-z.
  29. Leroux J., Abu Amara S., Lechevallier J. Legg-Calve-Perthes disease. Orthop Traumatol Surg. Res. 2018; 104(1S):S107-S112. doi: 10.1016/j. otsr.2017.04.012.
  30. Riabushko O.B., Yeroshenko G. A., Klepets O.V. et al. Vascular type of Ehlers-Danlos Syndrome - a Rare Monogenic Connective Tissue Disease. Bulletin of Problems Biology and Medicine. 2021; 12:84-90.
  31. Merla G., Brunetti-Pierri N., Piccolo P. et al. Supravalvular Aortic Stenosis. Circulation: Cardiovascular Genetics. 2012; 5(6): 692-96.
  32. Pons L., Bouvagnet P., Bakloul M. et al. Supravalvular Aortic Stenosis Caused by a Familial Chromosome 7 Inversion Disrupting the ELN Gene Uncovered by Whole-Genome Sequencing. Mol. Syndromol. 2019; 10(4): 209-13. doi: 10.1159/000500215.
  33. Mohamed M., Voet M., Gardeitchik T. et al. Cutis Laxa. Adv. Exp. Med. Biol. 2014; 802:161-84. doi: 10.1007/978-94-007-7893-1_11.
  34. Coelho S.G., Almeida A.G. Marfan syndrome revisited: From genetics to the clinic. Rev Port Cardiol (Engl Ed). 2020; 39(4):215-26. English, doi: 10.1016/j.repc.2019.09.008.
  35. Neuhann T.M. Hereditare Linsenluxation [Hereditary ectopia lentis]. Klin. Monbl. Augenheilkd. 2015; 232(3): 259-65. doi: 10.1055/s-0034-1383330.
  36. Knoll R., Postel R., Wang J. et al. Laminin-alpha4 and integrin-linked kinase mutations cause human cardiomyopathy via simultaneous defects in cardiomyocytes and endothelial cells. Circulation. 2007; 116(5): 515-25. doi: 10.1161/CIRCULATIONAHA.107.689984.
  37. Кенис В.М., Команцев В.Н., Димитриева А.Ю. и др. Синдром Шварца-Джампела: опыт диагностики и ортопедического лечения. Нервно-мышечные болезни. 2020;10 (2):53-59.
  38. Uchida N., Shibata H., Nishimura G. et al. A novel mutation in the ACAN gene in a family with autosomal dominant short stature and intervertebral disc disease. Hum. Genome Var. 2020;7(44). doi.:10.1038/ s41439-020-00132-8.
  39. Murphy-Ryan M., Psychogios A., Lindor N.M. Hereditary disorders of connective tissue: A guide to the emerging differential diagnosis. Genetics in Medicine. 2010; 12(6): 344-54. doi: 10.1097/gim.0b013e3181e074f0.
  40. Demak R. Marfan syndrome: a silent killer. Sports Illustr. 1986; 64:30-5.
  41. Cheng A., Owens D. Marfan syndrome, inherited aortopathies and exercise: What is the right answer? Br.J. Sports Med. 2016; 50:100-104.
  42. International Paralympic Committee of USA.
  43. Gavriilidou A., Galanis N., Gionis M. et al. Management of physical stress in young athletes suffering from connective tissue disorders induced by fibrillinopathies: The importance of ergophysiology. IOSR J. of Sports and Physical Education. 2017; 4(5): 16-26.
  44. Проект российских рекомендаций, наследственные и многофакторные нарушения соединительной ткани у детей алгоритмы диагностики, тактика ведения. Разработан комитетом экспертов педиатрической группы «дисплазия соединительной ткани» при российском научном обществе терапевтов. Педиатрия. 2014; 93(5): 4-40.
  45. Румянцева В.А., Заклязьминская Е.В. Клиническое и генетическое разнообразие наследственных дисплазий соединительной ткани. Журнал имени академика Б.В. Петровского. 2015; 2: 5-17.
  46. ICD-11 for Mortality and Morbidity Statistics.
  47. Тябут Т.Д., Каратыш О.М. Недифференцированная дисплазия соединительной ткани. Совpeменная ревматология. 2009; 3(2): 19-23.
  48. Тимохина В.Э., Мехдиева К.Р., Бляхман Ф.А. Дисплазия соединительной ткани у юных и молодых спортсменов: обзор литературы. Человек. Спорт. Медицина 2018; 18(3): 101-12.
  49. Ивянский С.А., Балыкова Л.А., Щекина Н.В. и др. Соединительнотканные дисплазии в спортивной практике. Consilium Medicum. Педиатрия (Прил.). 2016; 4: 48-55.
  50. Друк И.В., Нечаева Г.И., Осеева О.В. и др. Персонифицированная оценка риска развития неблагоприятных сердечнососудистых осложнений у пациентов молодого возраста с дисплазией соединительной ткани. Кардиология. 201 5;55:3: 25-84.
  51. Weber A.E, Bedi A., Tibor L.M et al. The hyperflexible hip: managing hip pain in the dancer and gymnast. Sports Health. 2015; 7: 346-58.
  52. Byrd J. W., John C. C., Kim Y-G. et al. Hip dysplasia in wrestlers: three lessons learned. J. of Hip Preservation Sur.2017; 4(4): 332-36 doi: 10.1093/jhps/hnx028.
  53. Frost H.M. Wolff's Law and bone's structural adaptations to mechanical usage: an overview for clinicians. Angle. Orthod. 1994; 64(3):175-88.
  54. Gong H., Zhu D., Gao J. et al. An adaptation model for trabecular bone at different mechanical levels. Biomed. Eng. Online. 2010; 9:32. doi: 10.1186/1475-925X-9-32.
  55. Mege R.M, Ladoux B. De l’irruption de la mecanique dans la chimie du vivant [The irruption of mechanics in the chemistry of life]. Med. Sci. (Paris). 2018; 34(11):963-71. French. doi: 10.1051/medsci/2018241.
  56. Davidson L.A. Mechanical design in embryos: mechanical signalling, robustness and developmental defects. Philos. Trans. R. Soc. Lond. B. Biol Sci. 2017; 372(1720): 20150516. doi: 10.1098/rstb.2015.0516.
  57. Miller C.J., Davidson L.A. The interplay between cell signalling and mechanics in developmental processes. Nat. Rev. Genet. 2013; 14(10):733-44. doi: 10.1038/nrg3513.
  58. Weaver V.M. Cell and tissue mechanics: the new cell biology frontier. Mol. Biol. Cell. 2017; 28(14):1815-18. doi: 10.1091/mbc.E17-05-0320.
  59. Ramage L.Integrins and extracellular matrix in mechanotransduction. Cell Health Cytoskelet. 2011; 4:1-9. doi: 10.2147/CHC.S21829.
  60. Wang J.H, Thampatty B.P. An introductory review of cell mechanobiology. Biomech. Model Mechanobiol. 2006; 5:1-16. doi: 10.1007/ s10237-005-0012-z.
  61. Plikus M.V., Wang, X., Sinha, S. et al. Fibroblasts: Origins, definitions, and functions in health and disease. Cell. 2021; 184(15): 3852-72. doi: 10.1016/j.cell.2021.06.024.
  62. Потехина Ю.П., Филатова А.И., Трегубова Е.С. и др. Механосенситивность различных клеток: возможная роль в регуляции и реализации эффектов физических методов лечения (обзор). Современные технологии в медицине. 2020; 12(4): 77-90. doi: 10.17691/stm2020.12.4.10.
  63. Lynch M.D., Watt F.M. Fibroblast heterogeneity: implications for human disease. J. Clin. Invest.2018; 128(1): 26-35. doi: 10.1172/JCI93555.
  64. Бозо И.Я., Деев Р.В., Пинаев Г.П. «Фибробласт» - специализированная клетка или функциональное состояние клеток мезенхимного происхождения? Цитология. 2010; 52(2): 99-109.
  65. Wang J. H-C., Thampatty B.P., Lin J-S. Mechanoregulation of gene expression in fibroblasts. Gene. 2007; 391(1-2): 1-15. doi: 10.1016/j.gene.2007.01.014.
  66. Dulauroy S., Di Carlo S.E., Langa F. et al. Lineage tracing and genetic ablation of ADAM12 (+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nat Med. 2012; 18(8): 1262-70. doi: 10.1038/nm.2848.
  67. Shi-Wen X., Renzoni E.A., Kennedy L. Endogenous endothelin-1 signaling contributes to type I collagen and CCN2 overexpression in fibrotic fibroblasts. Matrix Biol. 2007; 26, 625-32. doi: 10.1016/j.matbio.2007.06.003.
  68. Hinz B. The myofibroblast: paradigm for a mechanically active cell. J. of Biomechanics. 2010; 43(1 ):146-155. doi: 10.1016/j.jbiomech.2009.09.020.
  69. Tomasek J.J, Gabbiani G., Hinz B. et al. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat. Rev. Mol. Cell Biol. 2002; 3(5):349-63. doi: 10.1038/nrm809.
  70. Hinz B., Gabbiani G. Cell-matrix and cell-cell contacts of myofibroblasts: role in connective tissue remodeling. Thromb Haemost. 2003; 90(6):993-02. doi: 10.1160/TH03-05-0328.
  71. Yang M.T., Reich D.H., Chen C.S. Measurement and analysis of traction force dynamics in response to vasoactive agonists.Integr. Biol. (Camb). 2011; 3(6):663-74. doi: 10.1039/c0ib00156b.
  72. D’Urso M., Kurniawan N.A. Mechanical and Physical Regulation of Fibroblast-Myofibroblast Transition: From Cellular Mechanoresponse to Tissue Pathology. Front. Bioeng. Biotechnol. 2020. doi: 10.3389/fbioe.2020.609653.
  73. Wang J. H-C. Mechanobiology of tendon. J.Biomech. 2006; 39(9):1563-82. doi: 10.1016/j.jbiomech.2005.05.011.
  74. Bershadsky A.D., Balaban N.Q., Geiger B. Adhesion-dependent cell mechanosensitivity. Annu. Rev. Cell Dev. Biol. 2003;19: 677-95. doi: 10.1146/annurev.cellbio.19.111301.153011.
  75. MacKenna D., Summerour S.R., Villarreal F.J. Role of mechanical factors in modulating cardiac fibroblast function and extracellular matrix synthesis. Cardiovasc. Res. 2000; 46: 257-63. doi: 10.1146/annurev.cellbio.19.111301.153011.
  76. Zaidel-Bar R., Itzkovitz S., Ma’ayan A. et al. Functional atlas of the integrin adhesome. Nat. Cell Biol. 2007; 9(8): 858-67. doi: 10.1038/ncb0807-858.
  77. Teoh C.M, Tam J.K., Tran T.Integrin and GPCR crosstalk in the regulation of ASM contraction signaling in asthma. J. Allergy. 2012: 341282. doi: 10.1155/2012/341282.
  78. Nardone G., Oliver-De La Cruz, Vrbsky J. et al. YAP regulates cell mechanics by controlling focal adhesion assembly. Nat.Commun.2017; 8:15321. doi: 10.1038/ncomms15321.
  79. Geiger B., Yamada K.M. Molecular architecture and function of matrix adhesions. Cold Spring Harb Perspect Biol. 2011; 3(5):a005033.
  80. Пастушкова Л.Х., Колотева М.И., Гончарова А.Г. Изменения протеома крови космонавтов с микрои макрососудистыми травмами при перегрузках на заключительном этапе длительных космических полетов. Авиакосмическая и экологическая медицина. 2020; 54(5): 6-14.
  81. Pastushkova L.K., Kireev K.S., Kononikhin A.S. et al. Detection of renal tissue and urinary tract proteins in the human urine after space flight. PLoS One. 2013; 8(8): e71652. doi: 10.1371/journal.pone.0071652.
  82. Kononikhin A.S., Starodubtseva N.L., Pastushkova L.K. et al. Spaceflight induced changes in the human proteome. Expert. Rev. Proteomics. 2017;14 (1): 15-29. doi: 10.1080/14789450.2017.1258307.
  83. Buravkova L., Larina I., Andreeva E. et al. Microgravity Effects on the Matrisome. Cells. 2021; 10(9): 2226. doi: 10.3390/cells10092226.
  84. Schreiber T., Allenspach P., Seifert B. et al. Connective tissue adaptations in the fingers of performance sport climbers. Eur. J. Sport Sci. 2015; 15(8):696-702. doi: 10.1080/17461391.2015.1048747.
  85. Prakash A., Entwisle T., Schneider M. et al. Connective tissue injury in calf muscle tears and return to play: MRI correlation. Br.J. Sports Med. 2018; 52(14): 929-33. doi: 10.1136/bjsports-2017-098362.
  86. Renoux J., Brasseur J.L., Wagner M. et al. Ultrasound-detected connective tissue involvement in acute muscle injuries in elite athletes and return to play: The French National Institute of Sports (INSEP) study. J. Sci. Med. Sport. 2019; 22(6): 641-46. doi: 10.1016/j.jsams.2019.01.007.
  87. Angelina M. V., Leif E. P., David D et al. High Prevalence of Connective Tissue Gene Variants in Professional Ballet. The Am. J. of Sports Medicine. 2019; 5: 1-7. doi: 10.1177/0363546519887955.
  88. Artells R., Pruna R., Dellal A. et al. Elastin: a possible genetic biomarker for more severe ligament injuries in elite soccer. A pilot study. Muscles Ligaments Tendons J. 2016; 6(2): 188-92. doi: 10.11138/mltj/2016.6.2.188/.

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