Evidence map›Paper›PMID 37771244›Full record

ArticleAutophagy2024

Blocking glycosphingolipid production alters autophagy in osteoclasts and improves myeloma bone disease.

Houfu Leng, Anna Katharina Simon, Nicole J Horwood

Open access · hybridAbstract read
In one paragraph

Article in Autophagy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

12 citing papers in PubMed, 15 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Houfu LengKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, UK, OX3 7FY.ORCID 0000-0002-4023-8588
Anna Katharina SimonKennedy Institute of Rheumatology, University of Oxford, Roosevelt Drive, Oxford, UK, OX3 7FY.ORCID 0000-0002-4077-7995
Nicole J HorwoodNorwich Medical School, University of East Anglia, Rosalind Franklin Road, Norwich, UK, NR4 7UQ.ORCID 0000-0002-6344-1677
University of Oxford · GBUniversity of East Anglia · GB

Funding

Medical Research Council MC_PC_17174Medical Research Council MC_PC_18059Wellcome Trust
6 · The paper itself

Abstract

Glycosphingolipids (GSLs) are key constituents of membrane bilayers playing a role in structural integrity, cell signalling in microdomains, endosomes and lysosomes, and cell death pathways. Conversion of ceramide into GSLs is controlled by GCS (glucosylceramide synthase) and inhibitors of this enzyme for the treatment of lipid storage disorders and specific cancers. With a diverse range of functions attributed to GSLs, the ability of the GSC inhibitor, eliglustat, to reduce myeloma bone disease was investigated. In pre-clinical models of multiple myeloma, osteoclast-driven bone loss was reduced by eliglustat in a mechanistically separate manner to zoledronic acid, a bisphosphonate that prevents osteoclast-mediated bone destruction. Autophagic degradation of TNF receptor-associated factor 3 (TRAF3), a key step for osteoclast differentiation, was inhibited by eliglustat as evidenced by TRAF3 lysosomal and cytoplasmic accumulation. By altering GSL composition, eliglustat prevented lysosomal degradation whilst exogenous addition of missing GSLs rescued TRAF3 degradation to restore osteoclast formation in bone marrow cells from myeloma patients. This work highlights the clinical potential of eliglustat as a therapy for myeloma bone disease. Furthermore, using eliglustat as a lysosomal inhibitor in osteoclasts may widen its therapeutic uses to other bone disorders such as bone metastasis, osteoporosis and inflammatory bone loss.

Indexed as

AutophagyBone DiseasesGlycosphingolipidsLysosomesMultiple MyelomaOsteoclastsAnimalsGlucosyltransferasesHumansMicePyrrolidinesZoledronic AcideliglustatGlucosyltransferasesGlycosphingolipidsPyrrolidinesZoledronic AcidAutophagyglycosphingolipidmultiple myelomaosteoclastTRAF3

Identifiers

PMID37771244
PMCPMC11062377
OpenAlexW4387158054

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.