Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, 210009, Jiangsu, China.
Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, 210009, Jiangsu, China.
Cell Death Dis. 2020 Mar 18;11(3):193. doi: 10.1038/s41419-020-2386-3.
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.
肌腱干/祖细胞（TSPCs）衰老与肌腱老化之间的联系已得到充分认识。然而，TSPCs 衰老的细胞和分子机制仍不完全清楚。在本研究中，我们研究了水通道蛋白 1（AQP1）在 TSPCs 衰老中的作用。我们发现，AQP1 的表达随着肌腱老化过程中的年龄增长而下降。在衰老的 TSPCs 中，AQP1 的过表达显著减弱了 TSPCs 的衰老。此外，AQP1 的过表达还恢复了与年龄相关的自我更新、迁移和肌腱分化功能障碍。此外，我们证明 JAK-STAT 信号通路在衰老的 TSPCs 中被激活，AQP1 的过表达抑制了 JAK-STAT 信号通路的激活，这表明 AQP1 通过抑制 JAK-STAT 信号通路来减弱 TSPCs 的衰老和与年龄相关的功能障碍。总之，我们的研究结果表明 AQP1 在调节 TSPCs 衰老中起关键作用，并为拮抗肌腱老化提供了一个新的靶点。
