Evidence map›Paper›PMID 41194652›Full record

ArticleClinical and translational medicine2025

Altered nicotinamide adenine dinucleotide metabolism drives cartilage degeneration and osteoarthritis.

Xiaoxin Wu, Xiwei Fan, Manuel Plan, Terra Stark, Tim McCubbin, Roberto A Barrero, Maria Marinova, Michael J Bertoldo, Dale M Goss, Lindsay E Wu and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical and translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. 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

13 authors.

Xiaoxin WuCentre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland, Australia.
Xiwei FanCentre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland, Australia.
Manuel PlanAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.
Terra StarkAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.
Tim McCubbinAustralian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland, Brisbane, Queensland, Australia.
Roberto A BarreroeResearch Office, Queensland University of Technology, Brisbane, Queensland, Australia.
Maria MarinovaSchool of Biomedical Sciences, University of New South Wales (UNSW), Sydney, New South Wales, Australia.
Michael J BertoldoSchool of Biomedical Sciences, University of New South Wales (UNSW), Sydney, New South Wales, Australia.
Dale M GossSchool of Biomedical Sciences, University of New South Wales (UNSW), Sydney, New South Wales, Australia.
Lindsay E WuSchool of Biomedical Sciences, University of New South Wales (UNSW), Sydney, New South Wales, Australia.
Ross CrawfordCentre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland, Australia.
Xinzhan MaoDepartment of Orthopaedic Surgery, The Second Xiangya Hospital, Central South University, Changsha, China.
Indira PrasadamCentre for Biomedical Technologies, Queensland University of Technology, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0001-5057-2427

Funding

National Health and Medical Research Council APP1127821
6 · The paper itself

Abstract

backgroundWe previously conducted a comprehensive survey of energy metabolism in osteoarthritis (OA), revealing significant reductions of nicotinamide adenine dinucleotide (NAD

methodsWe conducted integrative analyses across human, murine, and rat OA models to examine NAD⁺ metabolism and its regulatory enzymes. The impact of pharmacological NAD⁺ augmentation (via nicotinamide mononucleotide (NMN) and nicotinamide riboside (NR)) and genetic overexpression of the NAD⁺ biosynthetic enzyme NMN adenosyltransferase (NMNAT1) was tested in surgical and aging-related OA models. Expression and function of the NAD⁺-consuming enzyme poly (ADP-ribose) polymerase 14 (PARP14) were examined via siRNA knockdown in chondrocytes under inflammatory conditions, coupled with metabolic assays and extracellular matrix gene profiling.

resultsNAD

conclusionsThis study reveals that dysregulated NAD⁺ metabolism, driven by increased PARP14 consumption, constitutes a potential mechanism underlying OA pathogenesis. Our findings support the concept that enhancing NAD⁺ availability via precursors or biosynthetic pathway modulation may offer disease-modifying effects at the molecular and histological level. Further investigation is needed to determine the functional and translational implications of targeting this pathway. KEY POINTS: PARP14 is upregulated in OA cartilage and contributes to NAD⁺ depletion. PARP14 silencing restores NAD⁺ levels and represses OA-related metabolic and matrix-degrading changes. NAD⁺ precursor treatment and NMNAT1 overexpression protect against cartilage degeneration in aging and post-traumatic OA models.

Indexed as

Cartilage, ArticularNADOsteoarthritisAnimalsChondrocytesDisease Models, AnimalFemaleHumansMaleMiceMice, Inbred C57BLNiacinamideNicotinamide MononucleotideNicotinamide-Nucleotide AdenylyltransferaseNicotinamide PhosphoribosyltransferasePoly(ADP-ribose) PolymerasesNADNiacinamideNicotinamide MononucleotideNicotinamide-Nucleotide AdenylyltransferaseNicotinamide PhosphoribosyltransferasePoly(ADP-ribose) PolymerasescartilagedegenerationNAD+osteoarthritis (OA)PARP14

Identifiers

PMID41194652
PMCPMC12589899

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.