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

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, Robert A. Rizza, Aleksey Matveyenko, Moustapha Kassem, Thomas Levin Andersen, Adrian Vella, Matthew T. Drake, Bart L. Clarke, Merry Jo Oursler, Sundeep Khosla

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number87
JournalNature communications
Volume11
Issue number1
DOIs
StatePublished - Dec 1 2020

Fingerprint

osteoblasts
Osteoblasts
metabolism
Osteoclasts
Energy Metabolism
bones
Dipeptidyl Peptidase 4
Bone
Bone and Bones
Bone Remodeling
calciferol
osteogenesis
homeostasis
sequencing
energy
glucose
laser induced fluorescence
ablation
peptides
RNA Sequence Analysis

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism. / Weivoda, Megan M.; Chew, Chee Kian; Monroe, David G.; Farr, Joshua N.; Atkinson, Elizabeth J.; Geske, Jennifer R.; Eckhardt, Brittany; Thicke, Brianne; Ruan, Ming; Tweed, Amanda J.; McCready, Louise K.; Rizza, Robert A.; Matveyenko, Aleksey; Kassem, Moustapha; Andersen, Thomas Levin; Vella, Adrian; Drake, Matthew T.; Clarke, Bart L.; Oursler, Merry Jo; Khosla, Sundeep.

In: Nature communications, Vol. 11, No. 1, 87, 01.12.2020.

Research output: Contribution to journalArticle

Weivoda, MM, Chew, CK, Monroe, DG, Farr, JN, Atkinson, EJ, Geske, JR, Eckhardt, B, Thicke, B, Ruan, M, Tweed, AJ, McCready, LK, Rizza, RA, Matveyenko, A, Kassem, M, Andersen, TL, Vella, A, Drake, MT, Clarke, BL, Oursler, MJ & Khosla, S 2020, 'Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism', Nature communications, vol. 11, no. 1, 87. https://doi.org/10.1038/s41467-019-14003-6
Weivoda, Megan M. ; Chew, Chee Kian ; Monroe, David G. ; Farr, Joshua N. ; Atkinson, Elizabeth J. ; Geske, Jennifer R. ; Eckhardt, Brittany ; Thicke, Brianne ; Ruan, Ming ; Tweed, Amanda J. ; McCready, Louise K. ; Rizza, Robert A. ; Matveyenko, Aleksey ; Kassem, Moustapha ; Andersen, Thomas Levin ; Vella, Adrian ; Drake, Matthew T. ; Clarke, Bart L. ; Oursler, Merry Jo ; Khosla, Sundeep. / Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism. In: Nature communications. 2020 ; Vol. 11, No. 1.
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