Skip to main content
SpringerLink
Log in

Targeting Senescent Tendon Stem/Progenitor Cells to Prevent or Treat Age-Related Tendon Disorders

  • Published:
Stem Cell Reviews and Reports Aims and scope Submit manuscript

Abstract

Age-related tendon disorder, a primary motor system disease, is characterized by biological changes in the tendon tissue due to senescence and seriously affects the quality of life of the elderly. The pathogenesis of this disease is not well-understood. Tendon stem/progenitor cells (TSPCs) exhibit multi-differentiation capacity. These cells are important cellular components of the tendon because of their roles in tendon tissue homeostasis, remodeling, and repair. Previous studies revealed alterations in the biological characteristics and tenogenic differentiation potential of TSPCs in senescent tendon tissue, in turn contributing to insufficient differentiation of TSPCs into tenocytes. Poor tendon repair can result in age-related tendinopathies. Therefore, targeting of senescent TSPCs may restore the tenogenic differentiation potential of these cells and achieve homeostasis of the tendon tissue to prevent or treat age-related tendinopathy. In this review, we summarize the biological characteristics of TSPCs and histopathological changes in age-related tendinopathy, as well as the potential mechanisms through which TSPCs contribute to senescence. This information may promote further exploration of innovative treatment strategies to rescue TSPCs from senescence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data Availability

Not applicable.

References

  1. Fuellen, G., et al. (2019). Health and Aging: unifying concepts, scores, biomarkers and pathways. Aging Dis, 10, 883–900.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Li, Y., et al. (2019). The potential roles of Tendon Stem/Progenitor cells in Tendon Aging. Curr Stem Cell Res Ther, 14, 34–42.

    Article  CAS  PubMed  Google Scholar 

  3. Zhang, Y. W., et al. (2022). Fecal microbiota transplantation ameliorates bone loss in mice with ovariectomy-induced osteoporosis via modulating gut microbiota and metabolic function. J Orthop Translat, 37, 46–60.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Almekinders, L. C., & Deol, G. (1999). The effects of aging, antiinflammatory drugs, and ultrasound on the in vitro response of tendon tissue. American Journal Of Sports Medicine, 27, 417–421.

    Article  CAS  PubMed  Google Scholar 

  5. Zhang, Y. W., et al. (2022). The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis. Crit Rev Food Sci Nutr, 1–19

  6. Zhang, X., et al. (2022). Clinical perspectives for repairing rotator cuff injuries with multi-tissue regenerative approaches. J Orthop Translat, 36, 91–108.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Lui, P. P. Y., & Wong, C. M. (2019). Biology of Tendon Stem cells and Tendon in Aging. Frontiers In Genetics, 10, 1338.

    Article  CAS  PubMed  Google Scholar 

  8. Birch, H. L., Peffers, M. J., & Clegg, P. D. (2016). Influence of Ageing on Tendon Homeostasis. Advances In Experimental Medicine And Biology, 920, 247–260.

    Article  CAS  PubMed  Google Scholar 

  9. Zhou, B., Zhou, Y., & Tang, K. (2014). An overview of structure, mechanical properties, and treatment for age-related tendinopathy. The Journal Of Nutrition, Health & Aging, 18, 441–448.

    Article  CAS  Google Scholar 

  10. Dunkman, A. A., et al. (2013). Decorin expression is important for age-related changes in tendon structure and mechanical properties. Matrix Biology, 32, 3–13.

    Article  CAS  PubMed  Google Scholar 

  11. Gehwolf, R., et al. (2016). Pleiotropic roles of the matricellular protein Sparc in tendon maturation and ageing. Scientific Reports, 6, 32635.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Delabastita, T., Bogaerts, S., & Vanwanseele, B. (2018). Age-Related Changes in Achilles Tendon Stiffness and Impact on Functional Activities: A Systematic Review and Meta-Analysis. J Aging Phys Act, 1–12

  13. Kostrominova, T. Y., & Brooks, S. V. (2013). Age-related changes in structure and extracellular matrix protein expression levels in rat tendons. Age (Dordr), 35, 2203–2214.

    Article  CAS  PubMed  Google Scholar 

  14. Arnesen, S. M., & Lawson, M. A. (2006). Age-related changes in focal adhesions lead to altered cell behavior in tendon fibroblasts. Mechanisms Of Ageing And Development, 127, 726–732.

    Article  CAS  PubMed  Google Scholar 

  15. Rui, Y. F., et al. (2011). Mechanical loading increased BMP-2 expression which promoted osteogenic differentiation of tendon-derived stem cells. Journal Of Orthopaedic Research, 29, 390–396.

    Article  CAS  PubMed  Google Scholar 

  16. Yu, T. Y., et al. (2013). Aging is associated with increased activities of matrix metalloproteinase-2 and – 9 in tenocytes. Bmc Musculoskeletal Disorders, 14, 2.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Rui, Y. F., Lui, P. P., Wong, Y. M., Tan, Q., & Chan, K. M. (2013). BMP-2 stimulated non-tenogenic differentiation and promoted proteoglycan deposition of tendon-derived stem cells (TDSCs) in vitro. Journal Of Orthopaedic Research, 31, 746–753.

    Article  CAS  PubMed  Google Scholar 

  18. Rui, Y. F., Lui, P. P., Wong, Y. M., Tan, Q., & Chan, K. M. (2013). Altered fate of tendon-derived stem cells isolated from a failed tendon-healing animal model of tendinopathy. Stem Cells And Development, 22, 1076–1085.

    Article  CAS  PubMed  Google Scholar 

  19. Jain, N. B., et al. (2019). Operative vs nonoperative treatment for atraumatic rotator cuff tears: a Trial Protocol for the arthroscopic rotator cuff pragmatic randomized clinical trial. JAMA Netw Open, 2, e199050.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Bechay, J., Lawrence, C., & Namdari, S. (2020). Calcific tendinopathy of the rotator cuff: a review of operative versus nonoperative management. Phys Sportsmed, 48, 241–246.

    Article  PubMed  Google Scholar 

  21. Xu, K., et al. (2021). Spironolactone Ameliorates Senescence and Calcification by Modulating Autophagy in Rat Tendon-Derived Stem Cells via the NF-kappaB/MAPK Pathway. Oxid Med Cell Longev 5519587 (2021).

  22. Zaseck, L. W., Miller, R. A., & Brooks, S. V. (2016). Rapamycin attenuates Age-associated changes in Tibialis Anterior Tendon Viscoelastic Properties. Journals Of Gerontology. Series A, Biological Sciences And Medical Sciences, 71, 858–865.

    Article  CAS  PubMed  Google Scholar 

  23. Bi, Y., et al. (2007). Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche. Nature Medicine, 13, 1219–1227.

    Article  CAS  PubMed  Google Scholar 

  24. Rajpar, I., & Barrett, J. G. (2020). Multi-differentiation potential is necessary for optimal tenogenesis of tendon stem cells. Stem Cell Research & Therapy, 11, 152.

    Article  CAS  Google Scholar 

  25. Wang, J. H., & Komatsu, I. (2016). Tendon Stem cells: Mechanobiology and Development of Tendinopathy. Advances In Experimental Medicine And Biology, 920, 53–62.

    Article  CAS  PubMed  Google Scholar 

  26. Kim, S. J., Song, D. H., & Kim, S. J. (2018). Characteristics of tendon derived stem cells according to different factors to induce the tendinopathy. Journal Of Cellular Physiology, 233, 6196–6206.

    Article  CAS  PubMed  Google Scholar 

  27. Rui, Y. F., et al. (2012). Expression of chondro-osteogenic BMPs in clinical samples of patellar tendinopathy. Knee Surgery, Sports Traumatology, Arthroscopy, 20, 1409–1417.

    Article  PubMed  Google Scholar 

  28. Rui, Y. F., et al. (2011). Does erroneous differentiation of tendon-derived stem cells contribute to the pathogenesis of calcifying tendinopathy? Chin Med J (Engl), 124, 606–610.

    PubMed  Google Scholar 

  29. Zhou, Z., et al. (2010). Tendon-derived stem/progenitor cell aging: defective self-renewal and altered fate. Aging Cell, 9, 911–915.

    Article  CAS  PubMed  Google Scholar 

  30. Kohler, J., et al. (2013). Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration. Aging Cell, 12, 988–999.

    Article  CAS  PubMed  Google Scholar 

  31. Zhang, J., & Wang, J. H. (2010). Mechanobiological response of tendon stem cells: implications of tendon homeostasis and pathogenesis of tendinopathy. Journal Of Orthopaedic Research, 28, 639–643.

    Article  PubMed  Google Scholar 

  32. Wood, L. K., & Brooks, S. V. (2016). Ten weeks of treadmill running decreases stiffness and increases collagen turnover in tendons of old mice. Journal Of Orthopaedic Research, 34, 346–353.

    Article  CAS  PubMed  Google Scholar 

  33. Dai, G., et al. (2020). Higher BMP expression in Tendon Stem/Progenitor cells contributes to the increased heterotopic ossification in Achilles Tendon with Aging. Front Cell Dev Biol, 8, 570605.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Wu, H., Zhao, G., Zu, H., Wang, J. H., & Wang, Q. M. (2015). Aging-related viscoelasticity variation of tendon stem cells (TSCs) characterized by quartz thickness shear mode (TSM) resonators. Sens Actuators (Warrendale Pa), 210, 369–380.

    Article  CAS  PubMed  Google Scholar 

  35. Zhang, J., Yuan, T., & Wang, J. H. (2016). Moderate treadmill running exercise prior to tendon injury enhances wound healing in aging rats. Oncotarget, 7, 8498–8512.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Tsai, W. C., et al. (2011). Decreased proliferation of aging tenocytes is associated with down-regulation of cellular senescence-inhibited gene and up-regulation of p27. Journal Of Orthopaedic Research, 29, 1598–1603.

    Article  CAS  PubMed  Google Scholar 

  37. Verzijl, N., et al. (2000). Effect of collagen turnover on the accumulation of advanced glycation end products. Journal Of Biological Chemistry, 275, 39027–39031.

    Article  CAS  PubMed  Google Scholar 

  38. Shinohara, I., et al. (2022). Biochemical markers of aging (Advanced Glycation End Products) and degeneration are increased in type 3 Rotator Cuff Tendon Stumps with increased Signal Intensity Changes on MRI. American Journal Of Sports Medicine, 50, 1960–1970.

    Article  PubMed  Google Scholar 

  39. Dai, J., Chen, H., & Chai, Y. (2019). Advanced Glycation End Products (AGEs) induce apoptosis of fibroblasts by activation of NLRP3 inflammasome via reactive oxygen species (ROS) signaling pathway. Medical Science Monitor, 25, 7499–7508.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Hegedus, E. J., et al. (2010). Vascularity and tendon pathology in the rotator cuff: a review of literature and implications for rehabilitation and surgery. British Journal Of Sports Medicine, 44, 838–847.

    Article  CAS  PubMed  Google Scholar 

  41. Vailas, A. C., Tipton, C. M., Laughlin, H. L., Tcheng, T. K., & Matthes, R. D. (1978). Physical activity and hypophysectomy on the aerobic capacity of ligaments and tendons. J Appl Physiol Respir Environ Exerc Physiol, 44, 542–546.

    CAS  PubMed  Google Scholar 

  42. Andarawis-Puri, N., Flatow, E. L., & Soslowsky, L. J. (2015). Tendon basic science: development, repair, regeneration, and healing. Journal Of Orthopaedic Research, 33, 780–784.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Tuite, D. J., Renstrom, P. A., & O’Brien, M. (1997). The aging tendon. Scandinavian Journal Of Medicine And Science In Sports, 7, 72–77.

    Article  CAS  PubMed  Google Scholar 

  44. Zhang, X., et al. (2016). Therapeutic Roles of Tendon Stem/Progenitor Cells in Tendinopathy. Stem Cells Int 4076578 (2016).

  45. Prasnikar, E., Borisek, J., & Perdih, A. (2021). Senescent cells as promising targets to tackle age-related diseases. Ageing Research Reviews, 66, 101251.

    Article  CAS  PubMed  Google Scholar 

  46. McHugh, D., & Gil, J. (2018). Senescence and aging: causes, consequences, and therapeutic avenues. Journal Of Cell Biology, 217, 65–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Wei, W., & Ji, S. (2018). Cellular senescence: molecular mechanisms and pathogenicity. Journal Of Cellular Physiology, 233, 9121–9135.

    Article  CAS  PubMed  Google Scholar 

  48. Gorgoulis, V., et al. (2019). Cellular Senescence: defining a path Forward. Cell, 179, 813–827.

    Article  CAS  PubMed  Google Scholar 

  49. Dai, G. C., Li, Y. J., Chen, M. H., Lu, P. P., & Rui, Y. F. (2019). Tendon stem/progenitor cell ageing: modulation and rejuvenation. World J Stem Cells, 11, 677–692.

    Article  PubMed  PubMed Central  Google Scholar 

  50. Chen, M., et al. (2020). AQP1 modulates tendon stem/progenitor cells senescence during tendon aging. Cell Death And Disease, 11, 193.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Hu, C., et al. (2017). Downregulation of CITED2 contributes to TGFbeta-mediated senescence of tendon-derived stem cells. Cell And Tissue Research, 368, 93–104.

    Article  CAS  PubMed  Google Scholar 

  52. Xu, H., & Liu, F. (2018). Downregulation of FOXP1 correlates with tendon stem/progenitor cells aging. Biochemical And Biophysical Research Communications, 504, 96–102.

    Article  CAS  PubMed  Google Scholar 

  53. Chen, L., et al. (2015). The role of Pin1 protein in aging of human tendon stem/progenitor cells. Biochemical And Biophysical Research Communications, 464, 487–492.

    Article  CAS  PubMed  Google Scholar 

  54. Herranz, N., & Gil, J. (2018). Mechanisms and functions of cellular senescence. J Clin Invest, 128, 1238–1246.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Chen, M., et al. (2021). Inhibition of JAK-STAT signaling pathway alleviates Age-Related phenotypes in Tendon Stem/Progenitor cells. Front Cell Dev Biol, 9, 650250.

    Article  PubMed  PubMed Central  Google Scholar 

  56. Chen, M., et al. (2021). Noncanonical Wnt5a signaling regulates tendon stem/progenitor cells senescence. Stem Cell Research & Therapy, 12, 544.

    Article  CAS  Google Scholar 

  57. Zhang, K., Asai, S., Yu, B., & Enomoto-Iwamoto, M. (2015). IL-1beta irreversibly inhibits tenogenic differentiation and alters metabolism in injured tendon-derived progenitor cells in vitro. Biochemical And Biophysical Research Communications, 463, 667–672.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Chen, S., et al. (2018). Interleukin-6 promotes proliferation but inhibits tenogenic differentiation via the Janus Kinase/Signal Transducers and Activators of transcription 3 (JAK/STAT3) pathway in Tendon-Derived stem cells. Medical Science Monitor, 24, 1567–1573.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Li, G., et al. (2021). Rejuvenation of senescent bone marrow mesenchymal stromal cells by Pulsed Triboelectric Stimulation. Adv Sci (Weinh), 8, e2100964.

    Article  PubMed  Google Scholar 

  60. Amano, H., et al. (2019). Telomere Dysfunction induces Sirtuin repression that drives Telomere-Dependent Disease. Cell Metab, 29, 1274–1290e1279.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Srinivas, N., Rachakonda, S., & Kumar, R. (2020). Telomeres and Telomere Length: A General Overview. Cancers (Basel)12

  62. Martinez, P., & Blasco, M. A. (2011). Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nature Reviews Cancer, 11, 161–176.

    Article  CAS  PubMed  Google Scholar 

  63. de Bernardes, B., & Blasco, M. A. (2013). Telomerase at the intersection of cancer and aging. Trends In Genetics, 29, 513–520.

    Article  Google Scholar 

  64. Kauppila, T. E. S., Kauppila, J. H. K., & Larsson, N. G. (2017). Mammalian Mitochondria and Aging: an update. Cell Metab, 25, 57–71.

    Article  CAS  PubMed  Google Scholar 

  65. Chen, H., et al. (2016). Autophagy prevents oxidative Stress-Induced loss of Self-Renewal Capacity and Stemness in Human Tendon Stem cells by reducing ROS Accumulation. Cellular Physiology And Biochemistry, 39, 2227–2238.

    Article  CAS  PubMed  Google Scholar 

  66. Lee, B. Y., et al. (2006). Senescence-associated beta-galactosidase is lysosomal beta-galactosidase. Aging Cell, 5, 187–195.

    Article  CAS  PubMed  Google Scholar 

  67. Hernandez-Segura, A., et al. (2017). Unmasking transcriptional heterogeneity in senescent cells. Current Biology, 27, 2652–2660e2654.

    Article  CAS  PubMed  Google Scholar 

  68. Wang, C., et al. (2022). Inhibition of IKKbeta/NF-kappaB signaling facilitates tendinopathy healing by rejuvenating inflamm-aging induced tendon-derived stem/progenitor cell senescence. Mol Ther Nucleic Acids, 27, 562–576.

    Article  CAS  PubMed  Google Scholar 

  69. Zhang, J., & Wang, J. H. (2015). Moderate Exercise mitigates the detrimental Effects of Aging on Tendon Stem cells. PLoS One, 10, e0130454.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Kiderlen, S., et al. (2019). Age related changes in cell stiffness of tendon stem/progenitor cells and a rejuvenating effect of ROCK-inhibition. Biochemical And Biophysical Research Communications, 509, 839–844.

    Article  CAS  PubMed  Google Scholar 

  71. Yin, H., et al. (2020). Three-dimensional self-assembling nanofiber matrix rejuvenates aged/degenerative human tendon stem/progenitor cells. Biomaterials, 236, 119802.

    Article  CAS  PubMed  Google Scholar 

  72. Yan, Z., et al. (2020). Aged Tendon Stem/Progenitor cells are less competent to form 3D Tendon Organoids due to Cell Autonomous and Matrix Production deficits. Frontiers In Bioengineering And Biotechnology, 8, 406.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Ruzzini, L., et al. (2014). Characterization of age-related changes of tendon stem cells from adult human tendons. Knee Surgery, Sports Traumatology, Arthroscopy, 22, 2856–2866.

    Article  PubMed  Google Scholar 

  74. Rui, Y. F., et al. (2019). CTGF Attenuates Tendon-Derived Stem/Progenitor Cell Aging. Stem Cells Int 6257537 (2019).

  75. Han, W., Tao, X., Weng, T., Chen, L., & Circular (2022). RNA PVT1 inhibits tendon stem/progenitor cell senescence by sponging microRNA-199a-5p. Toxicology In Vitro, 79, 105297.

    Article  CAS  PubMed  Google Scholar 

  76. Klatte-Schulz, F., et al. (2012). Influence of age on the cell biological characteristics and the stimulation potential of male human tenocyte-like cells. Eur Cell Mater, 24, 74–89.

    Article  CAS  PubMed  Google Scholar 

  77. Alberton, P., et al. (2015). Loss of tenomodulin results in reduced self-renewal and augmented senescence of tendon stem/progenitor cells. Stem Cells And Development, 24, 597–609.

    Article  CAS  PubMed  Google Scholar 

  78. Chen, J., et al. (2016). Characterization and comparison of post-natal rat Achilles tendon-derived stem cells at different development stages. Scientific Reports, 6, 22946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Chen, L., et al. (2015). miR-135a modulates tendon stem/progenitor cell senescence via suppressing ROCK1. Bone, 71, 210–216.

    Article  CAS  PubMed  Google Scholar 

  80. Nie, D., et al. (2021). Rapamycin Treatment of Tendon Stem/Progenitor Cells Reduces Cellular Senescence by Upregulating Autophagy. Stem Cells Int 6638249 (2021).

  81. Popov, C., Kohler, J., & Docheva, D. (2015). Activation of EphA4 and EphB2 Reverse Signaling restores the Age-Associated reduction of Self-Renewal, Migration, and actin turnover in human tendon Stem/Progenitor cells. Frontiers In Aging Neuroscience, 7, 246.

    Article  PubMed  Google Scholar 

  82. Jiang, D., Xu, B., & Gao, P. (2018). Effects of young extracellular matrix on the biological characteristics of aged tendon stem cells. Adv Clin Exp Med, 27, 1625–1630.

    Article  PubMed  Google Scholar 

  83. Han, W., Wang, B., Liu, J., & Chen, L. (2017). The p16/miR-217/EGR1 pathway modulates age-related tenogenic differentiation in tendon stem/progenitor cells. Acta Biochimica Et Biophysica Sinica (Shanghai), 49, 1015–1021.

    Article  CAS  Google Scholar 

  84. Tan, Q., Lui, P. P., Rui, Y. F., & Wong, Y. M. (2012). Comparison of potentials of stem cells isolated from tendon and bone marrow for musculoskeletal tissue engineering. Tissue Engineering Part A, 18, 840–851.

    Article  CAS  PubMed  Google Scholar 

  85. Zhang, C., et al. (2018). Histone deacetylase inhibitor treated cell sheet from mouse tendon stem/progenitor cells promotes tendon repair. Biomaterials, 172, 66–82.

    Article  CAS  PubMed  Google Scholar 

  86. Magne, D., & Bougault, C. (2015). What understanding tendon cell differentiation can teach us about pathological tendon ossification. Histology And Histopathology, 30, 901–910.

    CAS  PubMed  Google Scholar 

  87. O’Brien, E. J., Frank, C. B., Shrive, N. G., Hallgrimsson, B., & Hart, D. A. (2012). Heterotopic mineralization (ossification or calcification) in tendinopathy or following surgical tendon trauma. International Journal Of Experimental Pathology, 93, 319–331.

    Article  PubMed  PubMed Central  Google Scholar 

  88. Jiang, D., et al. (2014). Effect of young extrinsic environment stimulated by hypoxia on the function of aged tendon stem cell. Cell Biochemistry And Biophysics, 70, 967–973.

    Article  CAS  PubMed  Google Scholar 

  89. Xu, Y., & Murrell, G. A. (2008). The basic science of tendinopathy. Clinical Orthopaedics And Related Research, 466, 1528–1538.

    Article  PubMed  PubMed Central  Google Scholar 

  90. Schmitz, A. A., Govek, E. E., Bottner, B., & Van Aelst, L. (2000). Rho GTPases: signaling, migration, and invasion. Experimental Cell Research, 261, 1–12.

    Article  CAS  PubMed  Google Scholar 

  91. Kato, J. Y., Matsuoka, M., Polyak, K., Massague, J., & Sherr, C. J. (1994). Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27Kip1) of cyclin-dependent kinase 4 activation. Cell, 79, 487–496.

    Article  CAS  PubMed  Google Scholar 

  92. Istvanffy, R., et al. (2015). Stroma-derived connective tissue growth factor maintains cell cycle progression and repopulation activity of hematopoietic stem cells in Vitro. Stem Cell Reports, 5, 702–715.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Yuda, A., et al. (2015). Effect of CTGF/CCN2 on osteo/cementoblastic and fibroblastic differentiation of a human periodontal ligament stem/progenitor cell line. Journal Of Cellular Physiology, 230, 150–159.

    Article  CAS  PubMed  Google Scholar 

  94. Abdelmohsen, K., & Gorospe, M. (2015). Noncoding RNA control of cellular senescence. Wiley Interdiscip Rev RNA, 6, 615–629.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Arthur, A., et al. (2011). EphB/ephrin-B interactions mediate human MSC attachment, migration and osteochondral differentiation. Bone, 48, 533–542.

    Article  CAS  PubMed  Google Scholar 

  96. Moqbel, S. A. A., et al. (2020). Tectorigenin alleviates inflammation, apoptosis, and ossification in rat tendon-derived stem cells via modulating NF-Kappa B and MAPK pathways. Front Cell Dev Biol, 8, 568894.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Liu, C., et al. (2018). Tendon-Derived Stem Cell Differentiation in the Degenerative Tendon Microenvironment. Stem Cells Int 2613821 (2018).

  98. Zhang, J., & Wang, J. H. (2012). BMP-2 mediates PGE(2) -induced reduction of proliferation and osteogenic differentiation of human tendon stem cells. Journal Of Orthopaedic Research, 30, 47–52.

    Article  PubMed  Google Scholar 

  99. Ellis, S. J., & Tanentzapf, G. (2010). Integrin-mediated adhesion and stem-cell-niche interactions. Cell And Tissue Research, 339, 121–130.

    Article  CAS  PubMed  Google Scholar 

  100. Liu, C., Arnold, R., Henriques, G., & Djabali, K. (2019). Inhibition of JAK-STAT Signaling with Baricitinib Reduces Inflammation and Improves Cellular Homeostasis in Progeria Cells. Cells 8

  101. Xu, M., et al. (2015). JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. Proc Natl Acad Sci U S A, 112, E6301–6310.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Baker, D. J., et al. (2011). Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature, 479, 232–236.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  103. Baker, D. J., et al. (2016). Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature, 530, 184–189.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Xu, M., et al. (2015). Targeting senescent cells enhances adipogenesis and metabolic function in old age. Elife, 4, e12997.

    Article  PubMed  PubMed Central  Google Scholar 

  105. Ogrodnik, M., et al. (2017). Cellular senescence drives age-dependent hepatic steatosis. Nature Communications, 8, 15691.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Khosla, S., Farr, J. N., & Kirkland, J. L. (2018). Inhibiting Cellular Senescence: a New Therapeutic paradigm for age-related osteoporosis. Journal Of Clinical Endocrinology And Metabolism, 103, 1282–1290.

    Article  PubMed  PubMed Central  Google Scholar 

  107. Farr, J. N., et al. (2017). Targeting cellular senescence prevents age-related bone loss in mice. Nature Medicine, 23, 1072–1079.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Chang, J., et al. (2016). Clearance of senescent cells by ABT263 rejuvenates aged hematopoietic stem cells in mice. Nature Medicine, 22, 78–83.

    Article  CAS  PubMed  Google Scholar 

  109. Yosef, R., et al. (2016). Directed elimination of senescent cells by inhibition of BCL-W and BCL-XL. Nature Communications, 7, 11190.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Zhu, Y., et al. (2017). New agents that target senescent cells: the flavone, fisetin, and the BCL-XL inhibitors, A1331852 and A1155463. Aging (Albany NY), 9, 955–963.

    Article  PubMed  Google Scholar 

  111. Cho, H. H., et al. (2005). Induction of osteogenic differentiation of human mesenchymal stem cells by histone deacetylase inhibitors. Journal Of Cellular Biochemistry, 96, 533–542.

    Article  CAS  PubMed  Google Scholar 

  112. Zhang, Y. W., et al. (2022). A narrative review of the moderating effects and repercussion of exercise intervention on osteoporosis: ingenious involvement of gut microbiota and its metabolites. J Transl Med, 20, 490.

    Article  PubMed  PubMed Central  Google Scholar 

  113. Thampatty, B. P., & Wang, J. H. (2018). Mechanobiology of young and aging tendons: in vivo studies with treadmill running. Journal Of Orthopaedic Research, 36, 557–565.

    Google Scholar 

  114. Burton, D. G., & Krizhanovsky, V. (2014). Physiological and pathological consequences of cellular senescence. Cellular And Molecular Life Sciences, 71, 4373–4386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  115. Song, P., An, J., & Zou, M. H. (2020). Immune Clearance of Senescent Cells to Combat Ageing and Chronic Diseases. Cells 9

  116. Di Micco, R., Krizhanovsky, V., & Baker, D. (2021). d’Adda di Fagagna, F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nature Reviews Molecular Cell Biology, 22, 75–95.

    Article  PubMed  Google Scholar 

  117. Kim, K. M., et al. (2017). Identification of senescent cell surface targetable protein DPP4. Genes & Development, 31, 1529–1534.

    Article  Google Scholar 

  118. Sadelain, M., Riviere, I., & Riddell, S. (2017). Therapeutic T cell engineering. Nature, 545, 423–431.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Amor, C., et al. (2020). Senolytic CAR T cells reverse senescence-associated pathologies. Nature, 583, 127–132.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. Takahashi, K., & Yamanaka, S. (2006). Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell, 126, 663–676.

    Article  CAS  PubMed  Google Scholar 

  121. Lapasset, L., et al. (2011). Rejuvenating senescent and centenarian human cells by reprogramming through the pluripotent state. Genes & Development, 25, 2248–2253.

    Article  CAS  Google Scholar 

  122. Ocampo, A., et al. (2016). Vivo amelioration of Age-Associated. Hallmarks by Partial Reprogramming Cell, 167, 1719–1733e1712.

    CAS  PubMed  Google Scholar 

  123. Kim, S. J., Oh, H. W., Chang, J. W., & Kim, S. J. (2020). Recovery of Tendon Characteristics by Inhibition of Aberrant Differentiation of Tendon-Derived Stem Cells from Degenerative Tendinopathy. Int J Mol Sci 21

Download references

Acknowledgements

Not applicable.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81572187 and No.81871812); Natural Science Foundation of Jiangsu Province (BK20221462).

Author information

Author notes

  1. Hao Wang and Guang-Chun Dai have contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, School of Medicine, Zhongda Hospital, Southeast University, No. 87 Ding Jia Qiao, 210009, Nanjing, Jiangsu, PR China

    Hao Wang, Guang-Chun Dai, Ying-Juan Li, Min-Hao Chen, Pan-Pan Lu, Yuan-Wei Zhang, Ming -Zhang, Mu-Min Cao & Yun-Feng Rui

  2. Orthopaedic Trauma Institute, Southeast University, No. 87 Ding Jia Qiao, 210009, Nanjing, Jiangsu, PR China

    Hao Wang, Guang-Chun Dai, Ying-Juan Li, Min-Hao Chen, Pan-Pan Lu, Yuan-Wei Zhang, Mu-Min Cao & Yun-Feng Rui

  3. Trauma Center, School of Medicine, Zhongda Hospital, Southeast University, No. 87 Ding Jia Qiao, 210009, Nanjing, Jiangsu, PR China

    Hao Wang, Guang-Chun Dai, Ying-Juan Li, Min-Hao Chen, Pan-Pan Lu, Yuan-Wei Zhang, Mu-Min Cao & Yun-Feng Rui

Authors
  1. Hao Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guang-Chun Dai
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ying-Juan Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Min-Hao Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pan-Pan Lu
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Yuan-Wei Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ming -Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Mu-Min Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yun-Feng Rui
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Wang H and Dai GC completed most of the writing; Li YJ and Zhang M provided assistance with the writing and searched for relevant publications; Chen MH and Zhang YW prepared the figure; Lu PP and Cao MM provided input during drafting of the paper; Rui YF conceived the idea, revised and proofread the paper.

Corresponding author

Correspondence to Yun-Feng Rui.

Ethics declarations

Ethics Approval

Not applicable.

Consent to Participate

Not applicable.

Consent to Publish

Not applicable.

Institutional Review Board

Not applicable.

Informed Consent

Not applicable.

Conflict of Interest

The authors declare that they have no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material

Below is the link to the electronic supplementary material.

Supplementary Material 1

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wang, H., Dai, GC., Li, YJ. et al. Targeting Senescent Tendon Stem/Progenitor Cells to Prevent or Treat Age-Related Tendon Disorders. Stem Cell Rev and Rep 19, 680–693 (2023). https://doi.org/10.1007/s12015-022-10488-9

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12015-022-10488-9

Keywords

Search

Navigation