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

被引：43
作者：
Chen, Minhao [1 ,2 ,3 ]
Xiao, Longfei [1 ,2 ,3 ]
Dai, Guangchun [1 ,2 ,3 ]
Lu, Panpan [1 ,2 ,3 ]
Zhang, Yuanwei [1 ,2 ,3 ]
Li, Yingjuan [4 ]
Ni, Ming [5 ]
Rui, Yunfeng [1 ,2 ,3 ,6 ]
机构：
[1] Southeast Univ, Zhongda Hosp, Sch Med, Dept Orthopaed, Nanjing, Peoples R China
[2] Southeast Univ, Orthopaed Trauma Inst OTI, Nanjing, Peoples R China
[3] Southeast Univ, Zhongda Hosp, Trauma Ctr, Sch Med, Nanjing, Peoples R China
[4] Southeast Univ, Zhongda Hosp, Sch Med, Dept Geriatr, Nanjing, Peoples R China
[5] Chinese Peoples Liberat Army Gen Hosp, Med Ctr 1, Dept Orthoped, Beijing, Peoples R China
[6] China Orthoped Regenerat Med Grp, Hangzhou, Peoples R China
来源：
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY | 2021年 / 9卷
基金：
中国国家自然科学基金;
关键词：
tendon-derived stem; progenitor cells; tendon aging; senescence; JAK-STAT signaling pathway; AG490; MESENCHYMAL STEM-CELLS; SELF-RENEWAL; CELLULAR SENESCENCE; SECRETORY PHENOTYPE; JAK/STAT PATHWAY; CHRONIC INFLAMMATION; DIFFERENTIATION; DYNAMICS; IMMUNITY;
D O I：
10.3389/fcell.2021.650250
中图分类号：
Q2 [细胞生物学];
学科分类号：
071009 ; 090102 ;
摘要：
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.
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页数：14
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