AQP1 modulates tendon stem/progenitor cells senescence during tendon aging

Abstract

The link between tendon stem/progenitor cells (TSPCs) senescence and tendon aging has been well recognized. However, the cellular and molecular mechanisms of TSPCs senescence are still not fully understood. In present study, we investigated the role of Aquaporin 1 (AQP1) in TSPCs senescence. We showed that AQP1 expression declines with age during tendon aging. In aged TSPCs, overexpression of AQP1 significantly attenuated TSPCs senescence. In addition, AQP1 overexpression also restored the age-related dysfunction of self-renewal, migration and tenogenic differentiation. Furthermore, we demonstrated that the JAK-STAT signaling pathway is activated in aged TSPCs, and AQP1 overexpression inhibited the JAK-STAT signaling pathway activation which indicated that AQP1 attenuates senescence and age-related dysfunction of TSPCs through the repression of JAK−STAT signaling pathway. Taken together, our findings demonstrated the critical role of AQP1 in the regulation of TSPCs senescence and provided a novel target for antagonizing tendon aging.

Rapamycin Treatment of Tendon Stem/Progenitor Cells Reduces Cellular Senescence by Upregulating Autophagy

“…Additionally, upregulation of the senescence-associated β -galactosidase (SA- β -gal) activity and p21 and/or p16 Ink4a -mediated irreversible cell-cycle arrest are molecular indicators of senescence [ 5 ]. Importantly, it has been demonstrated that the number of senescent cells is positively associated with normal aging in various organs and tissues, including tendon [ 6 – 9 ].…”

Inhibition of JAK-STAT Signaling Pathway Alleviates Age-Related Phenotypes in Tendon Stem/Progenitor Cells

“…The RNA sequencing was performed by Beijing CapitalBio Corporation (Beijing, China) as previously described ( Chen et al, 2020 ). The libraries were generated using NEBNext Ultra RNA Library Prep Kit for Illumina and sequenced on the Illumina HiSeq 2500 platform.…”

“… Doles et al (2012) showed that increased JAK-STAT signaling inhibits hair follicle stem cell function in aged mice. In addition, our previous study has demonstrated that JAK-STAT signaling pathway is activated in TSPCs of Achilles tendon from aged rats ( Chen et al, 2020 ). Therefore, these findings prompted us to investigate the specific role of the JAK-STAT signaling pathway in TSPC aging and age-related dysfunction.…”

Tendon Stem/Progenitor Cell Subpopulations and Their Implications in Tendon Biology

“…These effects are at least partly caused by augmented Rho-associated protein kinases (ROCK), inhibition of which could restore the phenotype of aged TSPCs to one similar to young TSPCs ( Kohler et al, 2013 ; Kiderlen et al, 2019 ). Additionally, downregulation of nuclear regulator CITED2 and Aquaporin 1(AQP1) are also reported to be correlated with TSPCs aging ( Hu et al, 2017 ; Chen et al, 2020 ). Functionally incompetent aged TSPCs will assemble into a less cell-populated, poorly organized and biomechanically inferior three-dimensional tendon organoids ( Yan et al, 2020 ).…”