Tendon-derived Stem/progenitor Cell Aging: Defective Self-renewal and Altered Fate

Overview

Journal Aging Cell

Specialties Cell Biology
Geriatrics

Date 2010 Jun 24

PMID 20569237

Citations 107

Authors

Zuping Zhou

Takintope Akinbiyi

Lili Xu

Melissa Ramcharan

Daniel J Leong

Stephen J Ros

Alexis C Colvin

Mitchell B Schaffler

Robert J Majeska

Evan L Flatow

Hui B Sun

Affiliations

Soon will be listed here.

Abstract

Aging is a major risk factor for tendon injury and impaired tendon healing, but the basis for these relationships remains poorly understood. Here we show that rat tendon- derived stem ⁄ progenitor cells (TSPCs) differ in both self-renewal and differentiation capability with age. The frequency of TSPCs in tendon tissues of aged animals is markedly reduced based on colony formation assays. Proliferation rate is decreased, cell cycle progression is delayed and cell fate patterns are also altered in aged TSPCs. In particular, expression of tendon lineage marker genes is reduced while adipocytic differentiation increased. Cited2, a multi-stimuli responsive transactivator involved in cell growth and senescence, is also downregulated in aged TSPCs while CD44, a matrix assembling and organizing protein implicated in tendon healing, is upregulated, suggesting that these genes participate in the control of TSPC function.

Citing Articles

The role of different physical exercises as an anti-aging factor in different stem cells.

Xu J, Song Z Biogerontology. 2025; 26(2):63.

PMID: 40009244 DOI: 10.1007/s10522-025-10205-2.

Erroneous Differentiation of Tendon Stem/Progenitor Cells in the Pathogenesis of Tendinopathy: Current Evidence and Future Perspectives.

Gao Y, Wang H, Shi L, Lu P, Dai G, Zhang M Stem Cell Rev Rep. 2024; 21(2):423-453.

PMID: 39579294 DOI: 10.1007/s12015-024-10826-z.

Various Strategies of Tendon Stem/Progenitor Cell Reprogramming for Tendon Regeneration.

Ahn S Int J Mol Sci. 2024; 25(21).

PMID: 39519296 PMC: 11547070. DOI: 10.3390/ijms252111745.

Arif W, Narendran S, Kannan N, Ramasamy K, Veerappan M, Chidambaranathan G Indian J Ophthalmol. 2024; 72(Suppl 4):S688-S695.

PMID: 38623706 PMC: 11338411. DOI: 10.4103/IJO.IJO_2491_23.

Effect of Aging on Tendon Biology, Biomechanics and Implications for Treatment Approaches.

Kwan K, Ng K, Rao Y, Zhu C, Qi S, Tuan R Int J Mol Sci. 2023; 24(20).

PMID: 37894875 PMC: 10607611. DOI: 10.3390/ijms242015183.

References

Kannus P, Jozsa L . Histopathological changes preceding spontaneous rupture of a tendon. A controlled study of 891 patients. J Bone Joint Surg Am. 1991; 73(10):1507-25. View

Nishimura E, Granter S, Fisher D . Mechanisms of hair graying: incomplete melanocyte stem cell maintenance in the niche. Science. 2004; 307(5710):720-4. DOI: 10.1126/science.1099593. View

Kuo C, Tuan R . Mechanoactive tenogenic differentiation of human mesenchymal stem cells. Tissue Eng Part A. 2008; 14(10):1615-27. DOI: 10.1089/ten.tea.2006.0415. View

Magnusson S, Beyer N, Abrahamsen H, Aagaard P, Neergaard K, Kjaer M . Increased cross-sectional area and reduced tensile stress of the Achilles tendon in elderly compared with young women. J Gerontol A Biol Sci Med Sci. 2003; 58(2):123-7. DOI: 10.1093/gerona/58.2.b123. View

Delorme B, Charbord P . Culture and characterization of human bone marrow mesenchymal stem cells. Methods Mol Med. 2007; 140:67-81. DOI: 10.1007/978-1-59745-443-8_4. View

Vogel H . Influence of maturation and age on mechanical and biochemical parameters of connective tissue of various organs in the rat. Connect Tissue Res. 1978; 6(3):161-6. DOI: 10.3109/03008207809152626. View

Levi B, Morrison S . Stem cells use distinct self-renewal programs at different ages. Cold Spring Harb Symp Quant Biol. 2009; 73:539-53. DOI: 10.1101/sqb.2008.73.049. View

Sun H, Zhu Y, Yin T, Sledge G, Yang Y . MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity. Proc Natl Acad Sci U S A. 1998; 95(23):13555-60. PMC: 24857. DOI: 10.1073/pnas.95.23.13555. View

Ansorge H, Beredjiklian P, Soslowsky L . CD44 deficiency improves healing tendon mechanics and increases matrix and cytokine expression in a mouse patellar tendon injury model. J Orthop Res. 2009; 27(10):1386-91. PMC: 2810854. DOI: 10.1002/jor.20891. View

10.

Zhang J, Wang J . Characterization of differential properties of rabbit tendon stem cells and tenocytes. BMC Musculoskelet Disord. 2010; 11:10. PMC: 2822826. DOI: 10.1186/1471-2474-11-10. View

11.

Shukunami C, Takimoto A, Oro M, Hiraki Y . Scleraxis positively regulates the expression of tenomodulin, a differentiation marker of tenocytes. Dev Biol. 2006; 298(1):234-47. DOI: 10.1016/j.ydbio.2006.06.036. View

12.

Birch H, Bailey J, Bailey A, Goodship A . Age-related changes to the molecular and cellular components of equine flexor tendons. Equine Vet J. 1999; 31(5):391-6. DOI: 10.1111/j.2042-3306.1999.tb03838.x. View

13.

Kranc K, Schepers H, Rodrigues N, Bamforth S, Villadsen E, Ferry H . Cited2 is an essential regulator of adult hematopoietic stem cells. Cell Stem Cell. 2009; 5(6):659-65. PMC: 2828538. DOI: 10.1016/j.stem.2009.11.001. View

14.

Rui Y, Lui P, Li G, Fu S, Lee Y, Chan K . Isolation and characterization of multipotent rat tendon-derived stem cells. Tissue Eng Part A. 2009; 16(5):1549-58. DOI: 10.1089/ten.TEA.2009.0529. View

15.

Kranc K, Bamforth S, Braganca J, Norbury C, van Lohuizen M, Bhattacharya S . Transcriptional coactivator Cited2 induces Bmi1 and Mel18 and controls fibroblast proliferation via Ink4a/ARF. Mol Cell Biol. 2003; 23(21):7658-66. PMC: 207593. DOI: 10.1128/MCB.23.21.7658-7666.2003. View

16.

Kovacevic D, Rodeo S . Biological augmentation of rotator cuff tendon repair. Clin Orthop Relat Res. 2008; 466(3):622-33. PMC: 2505220. DOI: 10.1007/s11999-007-0112-4. View

17.

Lyons A . Analysing cell division in vivo and in vitro using flow cytometric measurement of CFSE dye dilution. J Immunol Methods. 2000; 243(1-2):147-54. DOI: 10.1016/s0022-1759(00)00231-3. View

18.

Couppe C, Hansen P, Kongsgaard M, Kovanen V, Suetta C, Aagaard P . Mechanical properties and collagen cross-linking of the patellar tendon in old and young men. J Appl Physiol (1985). 2009; 107(3):880-6. DOI: 10.1152/japplphysiol.00291.2009. View

19.

Perez A, Perrine M, Brainard N, Vogel K . Scleraxis (Scx) directs lacZ expression in tendon of transgenic mice. Mech Dev. 2003; 120(10):1153-63. DOI: 10.1016/j.mod.2003.08.003. View

20.

Chen Y, Haviernik P, Bunting K, Yang Y . Cited2 is required for normal hematopoiesis in the murine fetal liver. Blood. 2007; 110(8):2889-98. PMC: 2018670. DOI: 10.1182/blood-2007-01-066316. View