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

Minhao Chen; Minhao Chen; Minhao Chen; Longfei Xiao; Longfei Xiao; Longfei Xiao; Guangchun Dai; Guangchun Dai; Guangchun Dai; Panpan Lu; Panpan Lu; Panpan Lu; Yuanwei Zhang; Yuanwei Zhang; Yuanwei Zhang; Yingjuan Li; Ming Ni; Yunfeng Rui; Yunfeng Rui; Yunfeng Rui; Yunfeng Rui

doi:10.3389/fcell.2021.650250

Frontiers in Cell and Developmental Biology (Mar 2021)

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

Minhao Chen,
Minhao Chen,
Minhao Chen,
Longfei Xiao,
Longfei Xiao,
Longfei Xiao,
Guangchun Dai,
Guangchun Dai,
Guangchun Dai,
Panpan Lu,
Panpan Lu,
Panpan Lu,
Yuanwei Zhang,
Yuanwei Zhang,
Yuanwei Zhang,
Yingjuan Li,
Ming Ni,
Yunfeng Rui,
Yunfeng Rui,
Yunfeng Rui,
Yunfeng Rui

Affiliations

Minhao Chen: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Minhao Chen: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Minhao Chen: Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Longfei Xiao: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Longfei Xiao: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Longfei Xiao: Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Guangchun Dai: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Guangchun Dai: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Guangchun Dai: Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Panpan Lu: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Panpan Lu: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Panpan Lu: Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Yuanwei Zhang: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Yuanwei Zhang: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Yuanwei Zhang: Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Yingjuan Li: Department of Geriatrics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Ming Ni: Department of Orthopedics, The First Medical Center, Chinese PLA General Hospital, Beijing, China
Yunfeng Rui: Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Yunfeng Rui: Orthopaedic Trauma Institute (OTI), Southeast University, Nanjing, China
Yunfeng Rui: Trauma Center, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China
Yunfeng Rui: China Orthopedic Regenerative Medicine Group, Hangzhou, China

DOI: https://doi.org/10.3389/fcell.2021.650250
Journal volume & issue: Vol. 9

Abstract

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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.

Published in Frontiers in Cell and Developmental Biology

ISSN: 2296-634X (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Science: Biology (General)
Website: https://www.frontiersin.org/journals/cell-and-developmental-biology

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