Mechanical Overloading Induced-Activation of mTOR Signaling in Tendon Stem/Progenitor Cells Contributes to Tendinopathy Development

作者全名："Nie, Daibang; Zhou, Yiqin; Wang, Wang; Zhang, Jianying; Wang, James H-C"

作者地址："[Nie, Daibang; Wang, Wang] Chongqing Med Univ, Dept Immunol, Coll Basic Med, Chongqing, Peoples R China; [Nie, Daibang; Zhou, Yiqin; Zhang, Jianying; Wang, James H-C] Univ Pittsburgh, Dept Orthopaed Surg, MechanoBiol Lab, Pittsburgh, PA 15260 USA; [Zhou, Yiqin] Naval Med Univ, Dept Orthopaed, Shanghai Changzheng Hosp, Shanghai, Peoples R China; [Wang, James H-C] Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA; [Wang, James H-C] Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA"

通信作者："Zhang, JY; Wang, JHC (corresponding author), Univ Pittsburgh, Dept Orthopaed Surg, MechanoBiol Lab, Pittsburgh, PA 15260 USA.; Wang, JHC (corresponding author), Univ Pittsburgh, Dept Phys Med & Rehabil, Pittsburgh, PA 15260 USA.; Wang, JHC (corresponding author), Univ Pittsburgh, Dept Bioengn, Pittsburgh, PA 15260 USA."

来源：FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY

ESI学科分类：MOLECULAR BIOLOGY & GENETICS

WOS号：WOS:000679130100001

JCR分区：Q1

影响因子：5.5

年份：2021

卷号：9

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：mechanical loading; treadmill running; tendon stem cells; mTOR; rapamycin

摘要："Despite the importance of mechanical loading in tendon homeostasis and pathophysiology, the molecular responses involved in the mechanotransduction in tendon cells remain unclear. In this study, we found that in vitro mechanical loading activated the mammalian target of rapamycin (mTOR) in rat patellar tendon stem/progenitor cells (TSCs) in a stretching magnitude-dependent manner. Application of rapamycin, a specific inhibitor of mTOR, attenuated the phosphorylation of S6 and 4E-BP1 and as such, largely inhibited the mechanical activation of mTOR. Moreover, rapamycin significantly decreased the proliferation and non-tenocyte differentiation of PTSCs as indicated by the reduced expression levels of LPL, PPAR gamma, SOX-9, collagen II, Runx-2, and osteocalcin genes. In the animal studies, mice subjected to intensive treadmill running (ITR) developed tendon degeneration, as evidenced by the formation of round-shaped cells, accumulation of proteoglycans, and expression of SOX-9 and collagen II proteins. However, daily injections of rapamycin in ITR mice reduced all these tendon degenerative changes. Collectively, these findings suggest that mechanical loading activates the mTOR signaling in TSCs, and rapamycin may be used to prevent tendinopathy development by blocking non-tenocyte differentiation due to mechanical over-activation of mTOR in TSCs."

基金机构： [NIHRO1AR065949]

基金资助正文：This work was supported in part by NIHRO1AR065949 (JW).