Evidence map›Paper›PMID 37468461›Full record

ArticleCell death & disease2023

Loss of function mutation in Ank causes aberrant mineralization and acquisition of osteoblast-like-phenotype by the cells of the intervertebral disc.

Takashi Ohnishi, Victoria Tran, Kimheak Sao, Pranay Ramteke, William Querido, Ruteja A Barve, Koen van de Wetering, Makarand V Risbud

Open access · goldAbstract read
In one paragraph

Article in Cell death & disease, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
4.8field-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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Current research on the role of HIF in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026
    Review
  4. Human hip osteoarthritis-associatedbioRxiv : the preprint server for biology · 2026
    Article
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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

8 authors at 3 institutions in 2 countries.

Takashi OhnishiDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.ORCID 0000-0002-9228-7250
Victoria TranDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Kimheak SaoDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.ORCID 0000-0002-9164-1529
Pranay RamtekeDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
William QueridoDepartment of Bioengineering, Temple University, Philadelphia, PA, 19122, USA.
Ruteja A BarveDepartment of Genetics, Genome Technology Access Centre at the McDonnell Genome Institute, Washington University, School of Medicine, St. Louis, MO, 63110, USA.
Koen van de WeteringDepartment of Dermatology and Cutaneous Biology, Jefferson Institute of Molecular Medicine and PXE International Center of Excellence in Research and Clinical Care, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA.
Makarand V RisbudDepartment of Orthopaedic Surgery, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA, 19107, USA. makarand.risbud@jefferson.edu.ORCID 0000-0003-3913-0649
Thomas Jefferson University · USJames S. McDonnell Foundation · USTemple University · US

Funding

Role of HIF-1 in Intervertebral Disc FunctionR01AR055655 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V · 2008 to 2023
$6.1M
Targeting cell senescence in a novel model of spontaneous disc degenerationR01AG073349 · NIA · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V · 2021 to 2025
$3.0M
Pathogenesis of Inflammation-driven Intervertebral Disc Herniation: The Role of Syndecan 4R01AR074813 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI RISBUD, MAKARAND V · 2019 to 2023
$2.3M
Novel Treatments for PXER01AR072695 · NIAMS · THOMAS JEFFERSON UNIVERSITY · PI LI, QIAOLI, VAN DE WETERING, KOEN · 2018 to 2022
$1.7M
NIAMS NIH HHS R01 AR055655NIAMS NIH HHS R01 AR072695NIAMS NIH HHS R01 AR074813NIA NIH HHS R01 AG073349
6 · The paper itself

Abstract

Pathological mineralization of intervertebral disc is debilitating and painful and linked to disc degeneration in a subset of human patients. An adenosine triphosphate efflux transporter, progressive ankylosis (ANK) is a regulator of extracellular inorganic pyrophosphate levels and plays an important role in tissue mineralization. However, the function of ANK in intervertebral disc has not been fully explored. Herein we analyzed the spinal phenotype of Ank mutant mice (ank/ank) with attenuated ANK function. Micro-computed tomography and histological analysis showed that loss of ANK function results in the aberrant annulus fibrosus mineralization and peripheral disc fusions with cranial to caudal progression in the spine. Vertebrae in ank mice exhibit elevated cortical bone mass and increased tissue non-specific alkaline phosphatase-positive endplate chondrocytes with decreased subchondral endplate porosity. The acellular dystrophic mineral inclusions in the annulus fibrosus were localized adjacent to apoptotic cells and cells that acquired osteoblast-like phenotype. Fourier transform infrared spectral imaging showed that the apatite mineral in the outer annulus fibrosus had similar chemical composition to that of vertebral bone. Transcriptomic analysis of annulus fibrosus and nucleus pulposus tissues showed changes in several biological themes with a prominent dysregulation of BMAL1/CLOCK circadian regulation. The present study provides new insights into the role of ANK in the disc tissue compartments and highlights the importance of local inorganic pyrophosphate metabolism in inhibiting the mineralization of this important connective tissue.

Indexed as

CalcinosisIntervertebral DiscIntervertebral Disc DegenerationAnimalsDiphosphatesHumansLoss of Function MutationMicePhenotypePhosphate Transport ProteinsX-Ray Microtomographyank protein, mouseDiphosphatesPhosphate Transport Proteins

Identifiers

PMID37468461
PMCPMC10356955
OpenAlexW4384820659

What Socratic holds

Textmetadata
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 Socratic graph.