抑制JAK-STAT信号通路可减轻肌腱干/祖细胞的衰老相关表型。
Inhibition of JAK-STAT Signaling Pathway Alleviates Age-Related Phenotypes in Tendon Stem/Progenitor Cells.
作者信息
Chen Minhao, Xiao Longfei, Dai Guangchun, Lu Panpan, Zhang Yuanwei, Li Yingjuan, Ni Ming, Rui Yunfeng
机构信息
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China.
出版信息
Front Cell Dev Biol. 2021 Mar 29;9:650250. doi: 10.3389/fcell.2021.650250. eCollection 2021.
Diminished regeneration or healing capacity of tendon occurs during aging. It has been well demonstrated that tendon stem/progenitor cells (TSPCs) play a vital role in tendon maintenance and repair. Here, we identified an accumulation of senescent TSPCs in tendon tissue with aging. In aged TSPCs, the activity of JAK-STAT signaling pathway was increased. Besides, genetic knockdown of JAK2 or STAT3 significantly attenuated TSPC senescence in aged TSPCs. Pharmacological inhibition of JAK-STAT signaling pathway with AG490 similarly attenuated cellular senescence and senescence-associated secretory phenotype (SASP) of aged TSPCs. In addition, inhibition of JAK-STAT signaling pathway also restored the age-related dysfunctions of TSPCs, including self-renewal, migration, actin dynamics, and stemness. Together, our findings reveal the critical role of JAK-STAT signaling pathway in the regulation of TSPC aging and suggest an ideal therapeutic target for the age-related tendon disorders.
随着年龄增长，肌腱的再生或愈合能力会下降。已有充分证据表明，肌腱干/祖细胞（TSPCs）在肌腱的维持和修复中起着至关重要的作用。在此，我们发现随着年龄增长，肌腱组织中衰老的TSPCs会积累。在衰老的TSPCs中，JAK-STAT信号通路的活性增加。此外，JAK2或STAT3的基因敲低显著减弱了衰老TSPCs中的TSPC衰老。用AG490对JAK-STAT信号通路进行药理学抑制同样减弱了衰老TSPCs的细胞衰老和衰老相关分泌表型（SASP）。此外，抑制JAK-STAT信号通路还恢复了TSPCs与年龄相关的功能障碍，包括自我更新、迁移、肌动蛋白动力学和干性。总之，我们的研究结果揭示了JAK-STAT信号通路在调节TSPC衰老中的关键作用，并为与年龄相关的肌腱疾病提出了一个理想的治疗靶点。
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