IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v10y2019i1d10.1038_s41467-019-10677-0.html
   My bibliography  Save this article

TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis

Author

Listed:
  • Jinbo Li

    (University of Rochester Medical Center)

  • Akram Ayoub

    (University of Rochester Medical Center)

  • Yan Xiu

    (University of Rochester Medical Center
    University of Iowa)

  • Xiaoxiang Yin

    (University of Rochester Medical Center
    Henan University First Affiliated Hospital)

  • James O. Sanders

    (University of Rochester Medical Center
    University of North Carolina)

  • Addisu Mesfin

    (University of Rochester Medical Center)

  • Lianping Xing

    (University of Rochester Medical Center)

  • Zhenqiang Yao

    (University of Rochester Medical Center)

  • Brendan F. Boyce

    (University of Rochester Medical Center)

Abstract

Inflammaging induces osteoporosis by promoting bone destruction and inhibiting bone formation. TRAF3 limits bone destruction by inhibiting RANKL-induced NF-κB signaling in osteoclast precursors. However, the role of TRAF3 in mesenchymal progenitor cells (MPCs) is unknown. Mice with TRAF3 deleted in MPCs develop early onset osteoporosis due to reduced bone formation and enhanced bone destruction. In young mice TRAF3 prevents β-catenin degradation in MPCs and maintains osteoblast formation. However, TRAF3 protein levels decrease in murine and human bone samples during aging when TGFβ1 is released from resorbing bone. TGFβ1 induces degradation of TRAF3 in murine MPCs and inhibits osteoblast formation through GSK-3β-mediated degradation of β-catenin. Thus, TRAF3 positively regulates MPC differentiation into osteoblasts. TRAF3 deletion in MPCs activated NF-κB RelA and RelB to promote RANKL expression and enhance bone destruction. We conclude that pharmacologic stabilization of TRAF3 during aging could treat/prevent age-related osteoporosis by inhibiting bone destruction and promoting bone formation.

Suggested Citation

  • Jinbo Li & Akram Ayoub & Yan Xiu & Xiaoxiang Yin & James O. Sanders & Addisu Mesfin & Lianping Xing & Zhenqiang Yao & Brendan F. Boyce, 2019. "TGFβ-induced degradation of TRAF3 in mesenchymal progenitor cells causes age-related osteoporosis," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10677-0
    DOI: 10.1038/s41467-019-10677-0
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-10677-0
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-10677-0?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10677-0. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.