Evidence map›Paper›PMID 34220525›Full record

ArticleFrontiers in pharmacology2021

Urolithin A Protects Chondrocytes From Mechanical Overloading-Induced Injuries.

Yuchen He, Lauren Yocum, Peter G Alexander, Michael J Jurczak, Hang Lin

Open access · goldAbstract read
In one paragraph

Article in Frontiers in pharmacology, 2021. 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
2.0field-weighted citation impact, top 15% 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, 27 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Mechanical Stress Triggers Premature Senescence in Cardiac Fibroblasts.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025
    Article
  10. Forkhead box O proteins in chondrocyte aging and diseases.Journal of orthopaedic translation · 2025
    Review
  11. Review
  12. Review
  13. Review
  14. Article
  15. Development of a submicron emulsion-based delivery system to improve the anti-inflammatory activity of urolithin A.Journal of pharmacy & pharmaceutical sciences : a publication of the Canadian Society for Pharmaceutical Sciences, Societe canadienne des sciences pharmaceutiques · 2025
    Article
  16. Review
  17. Acupotomy alleviates knee osteoarthritis in rabbit by regulating chondrocyte mitophagy Pink1-Parkin pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2024
    Article
  18. Article
  19. Targeting therapy-induced senescence as a novel strategy to combat chemotherapy-induced peripheral neuropathy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024
    Review
  20. Review
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

5 authors at 2 institutions in 2 countries.

Yuchen HeDepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Lauren YocumDepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Peter G AlexanderDepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Michael J JurczakDivision of Endocrinology and Metabolism, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
Hang LinDepartment of Orthopaedic Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States.
University of Pittsburgh · USCentral South University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Physiological mechanical stimulation has been shown to promote chondrogenesis, but excessive mechanical loading results in cartilage degradation. Currently, the underlying mechanotransduction pathways in the context of physiological and injurious loading are not fully understood. In this study, we aim to identify the critical factors that dictate chondrocyte response to mechanical overloading, as well as to develop therapeutics that protect chondrocytes from mechanical injuries. Specifically, human chondrocytes were loaded in hyaluronic hydrogel and then subjected to dynamic compressive loading under 5% (DL-5% group) or 25% strain (DL-25% group). Compared to static culture and DL-5%, DL-25% reduced cartilage matrix formation from chondrocytes, which was accompanied by the increased senescence level, as revealed by higher expression of p21, p53, and senescence-associated beta-galactosidase (SA-β-Gal). Interestingly, mitophagy was suppressed by DL-25%, suggesting a possible role for the restoration mitophagy in reducing cartilage degeneration with mechanical overloading. Next, we treated the mechanically overloaded samples (DL-25%) with Urolithin A (UA), a natural metabolite previously shown to enhance mitophagy in other cell types. qRT-PCR, histology, and immunostaining results confirmed that UA treatment significantly increased the quantity and quality of cartilage matrix deposition. Interestingly, UA also suppressed the senescence level induced by mechanical overloading, demonstrating its senomorphic potential. Mechanistic analysis confirmed that UA functioned partially by enhancing mitophagy. In summary, our results show that mechanical overloading results in cartilage degradation partially through the impairment of mitophagy. This study also identifies UA's novel use as a compound that can protect chondrocytes from mechanical injuries, supporting high-quality cartilage formation/maintenance.

Indexed as

cartilagechondrocytemechanical loadingmitophagysenescenceurolithin A

Identifiers

PMID34220525
PMCPMC8245698
OpenAlexW3176458608

What OpenQuestion 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 OpenQuestion graph.