Transcriptomic profiling of the myeloma bone-lining niche reveals BMP signalling inhibition to improve bone disease

Sarah Gooding, Sam W. Z. Olechnowicz, Emma V. Morris, Andrew E. Armitage, Joao Arezes, Joe Frost, Emmanouela Repapi, James R. Edwards, Neil Ashley, Craig Waugh, Nicola Gray, Erik Martinez-Hackert, Pei Jin Lim, Sant-Rayn Pasricha, Helen Knowles, Adam J. Mead, Karthik Ramasamy, Hal Drakesmith () and Claire M. Edwards ()
Additional contact information
Sarah Gooding: University of Oxford
Sam W. Z. Olechnowicz: University of Oxford
Emma V. Morris: University of Oxford
Andrew E. Armitage: University of Oxford
Joao Arezes: University of Oxford
Joe Frost: University of Oxford
Emmanouela Repapi: University of Oxford
James R. Edwards: University of Oxford
Neil Ashley: University of Oxford
Craig Waugh: University of Oxford
Nicola Gray: University of Oxford
Erik Martinez-Hackert: Michigan State University
Pei Jin Lim: University of Oxford
Sant-Rayn Pasricha: University of Oxford
Helen Knowles: University of Oxford
Adam J. Mead: Oxford University Hospitals NHS Trust
Karthik Ramasamy: Oxford University Hospitals NHS Trust
Hal Drakesmith: University of Oxford
Claire M. Edwards: University of Oxford

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Multiple myeloma is an incurable, bone marrow-dwelling malignancy that disrupts bone homeostasis causing skeletal damage and pain. Mechanisms underlying myeloma-induced bone destruction are poorly understood and current therapies do not restore lost bone mass. Using transcriptomic profiling of isolated bone lining cell subtypes from a murine myeloma model, we find that bone morphogenetic protein (BMP) signalling is upregulated in stromal progenitor cells. BMP signalling has not previously been reported to be dysregulated in myeloma bone disease. Inhibition of BMP signalling in vivo using either a small molecule BMP receptor antagonist or a solubilized BMPR1a-FC receptor ligand trap prevents trabecular and cortical bone volume loss caused by myeloma, without increasing tumour burden. BMP inhibition directly reduces osteoclastogenesis, increases osteoblasts and bone formation, and suppresses bone marrow sclerostin levels. In summary we describe a novel role for the BMP pathway in myeloma-induced bone disease that can be therapeutically targeted.

Date: 2019
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-019-12296-1 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12296-1

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-019-12296-1

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().