Evidence map›Paper›PMID 30201038›Full record

ArticleArthritis research & therapy2018

Monosodium urate crystals reduce osteocyte viability and indirectly promote a shift in osteocyte function towards a proinflammatory and proresorptive state.

Ashika Chhana, Bregina Pool, Karen E Callon, Mei Lin Tay, David Musson, Dorit Naot, Geraldine McCarthy, Susan McGlashan, Jillian Cornish, Nicola Dalbeth

Open access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
2.5field-weighted citation impact, top 11% 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

28 citing papers in PubMed, 48 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. The pathogenesis of gout.Journal of rheumatic diseases · 2025
    Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Orthopaedic Management of Gout.Journal of the American Academy of Orthopaedic Surgeons. Global research & reviews · 2022
    Article
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article
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

10 authors at 2 institutions in 2 countries.

Ashika ChhanaDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand.
Bregina PoolDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand.
Karen E CallonDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand.
Mei Lin TayDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand.
David MussonDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand.
Dorit NaotDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand.
Geraldine McCarthyDepartment of Rheumatology, Mater Misericordiae University Hospital, Dublin, Ireland.
Susan McGlashanDepartment of Anatomy and Medical Imaging, University of Auckland, Auckland, New Zealand.
Jillian CornishDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand.
Nicola DalbethDepartment of Medicine, Bone & Joint Research Group, University of Auckland, Auckland, New Zealand. n.dalbeth@auckland.ac.nz.
University of Auckland · NZMater Misericordiae University Hospital · IE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBone erosion is a frequent complication of gout and is strongly associated with tophi, which are lesions comprising inflammatory cells surrounding collections of monosodium urate (MSU) crystals. Osteocytes are important cellular mediators of bone remodeling. The aim of this study was to investigate the direct effects of MSU crystals and indirect effects of MSU crystal-induced inflammation on osteocytes.

methodsFor direct assays, MSU crystals were added to MLO-Y4 osteocyte cell line cultures or primary mouse osteocyte cultures. For indirect assays, the RAW264.7 macrophage cell line was cultured with or without MSU crystals, and conditioned medium from these cultures was added to MLO-Y4 cells. MLO-Y4 cell viability was assessed using alamarBlue® and LIVE/DEAD® assays, and MLO-Y4 cell gene expression and protein expression were assessed by real-time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. Histological analysis was used to examine the relationship between MSU crystals, inflammatory cells, and osteocytes in human joints affected by tophaceous gout.

resultsIn direct assays, MSU crystals reduced MLO-Y4 cell and primary mouse osteocyte viability but did not alter MLO-Y4 cell gene expression. In contrast, conditioned medium from MSU crystal-stimulated RAW264.7 macrophages did not affect MLO-Y4 cell viability but significantly increased MLO-Y4 cell expression of osteocyte-related factors including E11, connexin 43, and RANKL, and inflammatory mediators such as interleukin (IL)-6, IL-11, tumor necrosis factor (TNF)-α and cyclooxygenase-2 (COX-2). Inhibition of COX-2 in MLO-Y4 cells significantly reduced the indirect effects of MSU crystals. In histological analysis, CD68

conclusionsMSU crystals directly inhibit osteocyte viability and, through interactions with macrophages, indirectly promote a shift in osteocyte function that favors bone resorption and inflammation. These interactions may contribute to disordered bone remodeling in gout.

Indexed as

AnimalsBone ResorptionCell SurvivalGoutHumansInflammation MediatorsMaleMiceMice, Inbred C57BLOsteocytesRatsRAW 264.7 CellsUric AcidInflammation MediatorsUric AcidBone erosionGoutInflammationOsteocyteUrate

Identifiers

PMID30201038
PMCPMC6131786
OpenAlexW2890708240

What OpenQuestion holds

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LicenceCC BY
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.