IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v11y2020i1d10.1038_s41467-019-14003-6.html
   My bibliography  Save this article

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism

Author

Listed:
  • Megan M. Weivoda

    (Mayo Clinic College of Medicine and Science
    University of Michigan School of Dentistry)

  • Chee Kian Chew

    (Mayo Clinic College of Medicine and Science
    Tan Tock Seng Hospital)

  • David G. Monroe

    (Mayo Clinic College of Medicine and Science)

  • Joshua N. Farr

    (Mayo Clinic College of Medicine and Science)

  • Elizabeth J. Atkinson

    (Mayo Clinic College of Medicine and Science)

  • Jennifer R. Geske

    (Mayo Clinic College of Medicine and Science)

  • Brittany Eckhardt

    (Mayo Clinic College of Medicine and Science)

  • Brianne Thicke

    (Mayo Clinic College of Medicine and Science)

  • Ming Ruan

    (Mayo Clinic College of Medicine and Science)

  • Amanda J. Tweed

    (Mayo Clinic College of Medicine and Science)

  • Louise K. McCready

    (Mayo Clinic College of Medicine and Science)

  • Robert A. Rizza

    (Mayo Clinic College of Medicine and Science)

  • Aleksey Matveyenko

    (Mayo Clinic College of Medicine and Science)

  • Moustapha Kassem

    (University of Southern Denmark
    Odense University Hospital)

  • Thomas Levin Andersen

    (University of Southern Denmark
    Odense University Hospital)

  • Adrian Vella

    (Mayo Clinic College of Medicine and Science)

  • Matthew T. Drake

    (Mayo Clinic College of Medicine and Science)

  • Bart L. Clarke

    (Mayo Clinic College of Medicine and Science)

  • Merry Jo Oursler

    (Mayo Clinic College of Medicine and Science)

  • Sundeep Khosla

    (Mayo Clinic College of Medicine and Science)

Abstract

Bone remodeling consists of resorption by osteoclasts followed by formation by osteoblasts, and osteoclasts are a source of bone formation-stimulating factors. Here we utilize osteoclast ablation by denosumab (DMAb) and RNA-sequencing of bone biopsies from postmenopausal women to identify osteoclast-secreted factors suppressed by DMAb. Based on these analyses, LIF, CREG2, CST3, CCBE1, and DPP4 are likely osteoclast-derived coupling factors in humans. Given the role of Dipeptidyl Peptidase-4 (DPP4) in glucose homeostasis, we further demonstrate that DMAb-treated participants have a significant reduction in circulating DPP4 and increase in Glucagon-like peptide (GLP)-1 levels as compared to the placebo-treated group, and also that type 2 diabetic patients treated with DMAb show significant reductions in HbA1c as compared to patients treated either with bisphosphonates or calcium and vitamin D. Thus, our results identify several coupling factors in humans and uncover osteoclast-derived DPP4 as a potential link between bone remodeling and energy metabolism.

Suggested Citation

  • Megan M. Weivoda & Chee Kian Chew & David G. Monroe & Joshua N. Farr & Elizabeth J. Atkinson & Jennifer R. Geske & Brittany Eckhardt & Brianne Thicke & Ming Ruan & Amanda J. Tweed & Louise K. McCready, 2020. "Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-019-14003-6
    DOI: 10.1038/s41467-019-14003-6
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-019-14003-6
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-019-14003-6?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
    ---><---

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Fenli Shao & Qianqian Liu & Yuyu Zhu & Zhidan Fan & Wenjun Chen & Shijia Liu & Xiaohui Li & Wenjie Guo & Gen-Sheng Feng & Haiguo Yu & Qiang Xu & Yang Sun, 2021. "Targeting chondrocytes for arresting bony fusion in ankylosing spondylitis," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Dominik Saul & Robyn Laura Kosinsky & Elizabeth J. Atkinson & Madison L. Doolittle & Xu Zhang & Nathan K. LeBrasseur & Robert J. Pignolo & Paul D. Robbins & Laura J. Niedernhofer & Yuji Ikeno & Diana , 2022. "A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

    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:11:y:2020:i:1:d:10.1038_s41467-019-14003-6. 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.