Activation of EphA4 and EphB2 Reverse Signaling Restores the Age-Associated Reduction of Self-Renewal, Migration, and Actin Turnover in Human Tendon Stem/Progenitor Cells

Frontiers in Aging Neuroscience
Cvetan PopovDenitsa Docheva

Abstract

Tendon tissues, due to their composition and function, are prone to suffer age-related degeneration and diseases as well as to respond poorly to current repair strategies. It has been suggested that local stem cells, named tendon stem/progenitor cells (TSPCs), play essential roles in tendon maintenance and healing. Recently, we have shown that TSPC exhibit a distinct age-related phenotype involving transcriptomal shift, poor self-renewal, and elevated senescence coupled with reduced cell migration and actin dynamics. Here, we report for the first time the significant downregulation of the ephrin receptors EphA4, EphB2 and B4 and ligands EFNB1 in aged-TSPC (A-TSPC). Rescue experiments, by delivery of target-specific clustered proteins, revealed that activation of EphA4- or EphB2-dependent reverse signaling could restore the migratory ability and normalize the actin turnover of A-TSPC. However, only EphA4-Fc stimulation improved A-TSPC cell proliferation to levels comparable to young-TSPC (Y-TSPC). Hence, our novel data suggests that decreased expression of ephrin receptors during tendon aging and degeneration limits the establishment of appropriate cell-cell interactions between TSPC and significantly diminished their proliferat...Continue Reading

References

Aug 25, 1999·Anatomy and Embryology·D D'Souza, K Patel
Jun 17, 2003·Journal of Cell Science·Keith K Murai, Elena B Pasquale
Sep 16, 2003·Nature Cell Biology·Daniel J MarstonCatherine D Nobes
Aug 8, 2006·Cell Metabolism·Chen ZhaoKoichi Matsuo
Dec 13, 2006·Journal of Cellular Physiology·Yoshiteru KajikawaToshikazu Kubo
Apr 11, 2007·Trends in Cell Biology·Joaquim Egea, Rüdiger Klein
Aug 21, 2007·Current Pharmaceutical Design·J DuD W Sretavan
Jan 2, 2009·Journal of Cell Science·Tohru YamazakiYoshiro Maru
Feb 25, 2010·Nature Reviews. Cancer·Elena B Pasquale
Sep 3, 2010·Current Opinion in Cell Biology·Maria Genander, Jonas Frisén
Mar 19, 2011·Circulation Research·Polina GoichbergAnnarosa Leri
Aug 3, 2011·Current Opinion in Cell Biology·Klemens Rottner, Theresia E B Stradal
Nov 11, 2011·Development·Danny A StarkD D W Cornelison
Jul 1, 2009·Sports Health·Christopher Kaeding, Thomas M Best
Jan 9, 2013·Journal of Animal Science·J Li, S E Johnson
Aug 29, 2013·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Virginia StiffelK-H William Lau
Apr 30, 2015·Journal of Biochemistry·Shingo TakeuchiManabu Negishi

❮ Previous
Next ❯

Citations

Mar 29, 2019·Journal of Orthopaedic Research : Official Publication of the Orthopaedic Research Society·Caleb GroteJinxi Wang
Aug 7, 2017·Graefe's Archive for Clinical and Experimental Ophthalmology = Albrecht Von Graefes Archiv Für Klinische Und Experimentelle Ophthalmologie·Christian WertheimerRicarda G Schumann
Jun 9, 2020·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Javier García-CecaAgustín G Zapata
Jun 24, 2020·Expert Opinion on Biological Therapy·Filippo MiglioriniNicola Maffulli
Mar 20, 2020·Cell Death & Disease·Minhao ChenYunfeng Rui
Feb 6, 2020·Frontiers in Genetics·Pauline Po Yee Lui, Chi Ming Wong
Oct 17, 2019·World Journal of Stem Cells·Guang-Chun DaiYun-Feng Rui
Dec 13, 2019·Stem Cells International·Yun-Feng RuiGuang-Chun Dai
Mar 3, 2021·Stem Cell Reviews and Reports·Bing Wei, Jun Lu
Aug 17, 2021·Frontiers in Medicine·Zhi Jie LiYou Lang Zhou

❮ Previous
Next ❯

Methods Mentioned

BETA
biopsies
PCR
GTPase

Software Mentioned

ImageProPlus4
ImageJ
GraphPad
AxioVisionLE
GraphPrism

Related Concepts

Related Feeds

Aging Genetics (Keystone)

This feed focuses on aging epidemiology and genetic, epigenetic, and proteomic aspects underlying aging, as well as aging- associated biomarkers. Here the latest research in this domain.

Cell Migration

Cell migration is involved in a variety of physiological and pathological processes such as embryonic development, cancer metastasis, blood vessel formation and remoulding, tissue regeneration, immune surveillance and inflammation. Here is the latest research.