Evidence map›Paper›PMID 26395178›Full record

ArticleArthritis research & therapy2015

Overexpression of MMP13 in human osteoarthritic cartilage is associated with the SMAD-independent TGF-β signalling pathway.

Erfan Aref-Eshghi, Ming Liu, Patricia E Harper, Jules Doré, Glynn Martin, Andrew Furey, Roger Green, Proton Rahman, Guangju Zhai

Registry-linked trialOpen access · goldAbstract read
In one paragraph

Article in Arthritis research & therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03665116 (Effects of Arginine on Osteoarthritis), which is not on this map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.2field-weighted citation impact, top 9% 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.

NCT03665116 naunknown statusnot on this mapstarted 2019, after this paper: background citation

Effects of Arginine on Osteoarthritis: A Pilot Clinical Trial

TypeinterventionalSponsorMemorial University of NewfoundlandRan2019 to 2024Enrolled38ConditionsKnee OsteoarthritisArmsL-arginine
3 · Its place in the literature

Who cites it

23 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
  2. Journal of clinical medicine · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Healthcare and Scientific Treatment of Knee Osteoarthritis.Journal of healthcare engineering · 2022
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. International journal of molecular sciences · 2019
    Article
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  19. Article
  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

9 authors at 1 institution in 2 countries.

Erfan Aref-EshghiDiscipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. erfanae@mun.ca.
Ming LiuDiscipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. ming.liu@med.mun.ca.
Patricia E HarperDiscipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. peh318@mun.ca.
Jules DoréDivision of Biomedical Science, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. jdore@mun.ca.
Glynn MartinDivision of Orthopedics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. gmartin@munmed.ca.
Andrew FureyDivision of Orthopedics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. andrewfurey@hotmail.com.
Roger GreenDiscipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. rcgreen@mun.ca.
Proton RahmanDiscipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. prahman@mun.ca.
Guangju ZhaiDiscipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, A1B 3V6, Canada. guangju.zhai@med.mun.ca.
Memorial University of Newfoundland · CA

Funding

Canadian Institutes of Health Research
6 · The paper itself

Abstract

introductionIn vitro and animal model of osteoarthritis (OA) studies suggest that TGF-β signalling is involved in OA, but human data is limited. We undertook this study to elucidate the role of TGF-β signalling pathway in OA by comparing the expression levels of TGFB1 and BMP2 as ligands, SMAD3 as an intracellular mediator, and MMP13 as a targeted gene between human osteoarthritic and healthy cartilage.

methodsHuman cartilage samples were collected from patients undergoing total hip/knee joint replacement surgery due to primary OA or hip fractures as controls. RNA was extracted from the cartilage tissues. Real-time quantitative PCR was performed to measure gene expression. Mann-Whitney test was utilized to compare the expression levels of TGFB1, BMP2, SMAD3 and MMP13 in human cartilage between OA cases and controls. Spearman's rank correlation coefficient (rho) was calculated to examine the correlation between the expression levels of the four genes studied and non-parametric regression was used to adjust for covariates.

resultsA total of 32 OA cases (25 hip OA and 7 knee OA) and 21 healthy controls were included. The expression of TGFB1, SMAD3, and MMP13 were on average 70%, 46%, and 355% higher, respectively, whereas the expression of BMP2 was 88% lower, in OA-affected cartilage than that of controls (all p < 0.03), but no difference was observed between hip and knee OA (all p > 0.4). The expression of TGFB1 was correlated with the expression of SMAD3 (rho = 0.50, p = 0.003) and MMP13 (rho = 0.46, p = 0.007) in OA-affected cartilage and the significance became stronger after adjustment for age, sex, and BMI. The expression of BMP2 was negatively correlated with both TGFB1 (rho = -0.50, p = 0.02) and MMP13 (rho = -0.48, p = 0.02) in healthy cartilage, but the significance was altered after adjustment for the covariates. There was no correlation between the expression of SMAD3 and MMP13.

conclusionsOur results demonstrate that MMP13 expression is associated with an increased expression of TGFB1 in OA-affected cartilage, possibly through SMAD-independent TGF-β pathway. Furthermore, TGF-β/SMAD3 is overactivated in OA cartilage; yet, the consequence of this overactivation remains to be established.

Indexed as

Gene ExpressionAgedAged, 80 and overBone Morphogenetic Protein 2Cartilage, ArticularFemaleHumansMaleMatrix Metalloproteinase 13Middle AgedOsteoarthritis, HipOsteoarthritis, KneeReverse Transcriptase Polymerase Chain ReactionSignal TransductionSmad3 ProteinTransforming Growth Factor beta1BMP2 protein, humanBone Morphogenetic Protein 2Matrix Metalloproteinase 13Smad3 ProteinTGFB1 protein, humanTransforming Growth Factor beta1

Identifiers

PMID26395178
PMCPMC4579831
OpenAlexW1954587332

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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.