Evidence map›Paper›PMID 37356505›Full record

ArticleArthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association2024

Human Rotator Cuff Tears Reveal an Age-Dependent Increase in Markers of Cellular Senescence and Selective Removal of Senescent Cells With Dasatinib + Quercetin Increases Genetic Expression of COL1A1 In Vitro.

Benjamin C Hawthorne, Ian J Wellington, Joshua T Sabitsky, Kyle V Murphy, Owen P Karsmarski, Rohin O Thomas, Matthew R LeVasseur, Michael R Mancini, Maxwell T Trudeau, Sagar Gulati and 4 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
5.1field-weighted citation impact, top 4% 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

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

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. The Role of Renal Cell Senescence in Diabetic Kidney Disease: Mechanisms and Therapeutic Advances.Diabetes, metabolic syndrome and obesity : targets and therapy · 2025
    Review
  7. Article
  8. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors at 2 institutions in 1 country.

Benjamin C HawthorneDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.. Electronic address: bhawthorne@uchc.edu.
Ian J WellingtonDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Joshua T SabitskyDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Kyle V MurphyDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Owen P KarsmarskiDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Rohin O ThomasDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Matthew R LeVasseurDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Michael R ManciniDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Maxwell T TrudeauDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Sagar GulatiDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Mary Beth R McCarthyDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Mark P CoteDepartment of Orthopaedic Surgery, University of Connecticut, Farmington, Connecticut, U.S.A.
Ming XuUConn Center on Aging, University of Connecticut School of Medicine, Farmington, Connecticut, U.S.A.
Augustus D MazzoccaDepartment of Orthopaedic Surgery, Massachusetts General Hospital, Boston, Massachusetts, U.S.A.; Massachusetts General Brigham Sports Medicine, Harvard Medical School, Boston, Massachusetts, U.S.A.
University of Connecticut · USMassachusetts General Hospital · US

Funding

Reciprocal Modulation of the Microbiome and Cellular Senescence in Metabolic DysfunctionR01AG068860 · NIA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI XU, MING, ZHOU, YANJIAO · 2020 to 2024
$2.8M
Targeting p21-Highly Expressing Cells to Increase Lifespan and Healthspan in Old AgeR01AG076642 · NIA · UNIVERSITY OF MINNESOTA · PI Ming Xu · 2022 to 2026
$2.4M
Targeting p21-positive Senescent Cells in vivo for Alleviating Metabolic and Physical DysfunctionR01AG066679 · NIA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI XU, MING · 2020 to 2024
$2.2M
Can Senolytics Improve the Aged Response to Viral InfectionR21AG071292 · NIA · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI HAYNES, LAURA, XU, MING · 2021 to 2022
$451k
NIA NIH HHS R01 AG066679NIA NIH HHS R01 AG068860NIA NIH HHS R01 AG076642NIA NIH HHS R21 AG071292
6 · The paper itself

Abstract

purposeTo quantify cellular senescence in supraspinatus tendon and subacromial bursa of humans with rotator cuff tears and to investigate the in vitro efficacy of the senolytic dasatinib + quercetin (D+Q) to eliminate senescent cells and alter tenogenic differentiation.

methodsTissue was harvested from 41 patients (mean age, 62 years) undergoing arthroscopic rotator cuff repairs. In part 1 (n = 35), senescence was quantified using immunohistochemistry and gene expression for senescent cell markers (p16 and p21) and the senescence-associated secretory phenotype (SASP) (interleukin [IL] 6, IL-8, matrix metalloproteinase [MMP] 3, monocyte chemoattractant protein [MCP] 1). Senescence was compared between patients <60 and ≥60 years old. In part 2 (n = 6) , an in vitro model of rotator cuff tears was treated with D+Q or control. D+Q, a chemotherapeutic and plant flavanol, respectively, kill senescent cells. Gene expression analysis assessed the ability of D+Q to kill senescent cells and alter markers of tenogenic differentiation.

resultsPart 1 revealed an age-dependent significant increase in the relative expression of p21, IL-6, and IL-8 in tendon and p21, p16, IL-6, IL-8, and MMP-3 in bursa (P < .05). A significant increase was seen in immunohistochemical staining of bursa p21 (P = .028). In part 2, D+Q significantly decreased expression of p21, IL-6, and IL-8 in tendon and p21 and IL-8 in bursa (P < .05). Enzyme-linked immunosorbent assay analysis showed decreased release of the SASP (IL-6, MMP-3, MCP-1; P = .002, P = .024, P < .001, respectively). Tendon (P = .022) and bursa (P = .027) treated with D+Q increased the expression of COL1A1.

conclusionsWhile there was an age-dependent increase in markers of cellular senescence, this relationship was not consistently seen across all markers and tissues. Dasatinib + quercetin had moderate efficacy in decreasing senescence in these tissues and increasing COL1A1 expression. CLINICAL RELEVANCE: This study reveals that cellular senescence may be a therapeutic target to alter the biological aging of rotator cuffs and identifies D+Q as a potential therapy.

Indexed as

Rotator Cuff InjuriesCellular SenescenceDasatinibHumansInterleukin-6Interleukin-8Matrix Metalloproteinase 3Middle AgedQuercetinDasatinibInterleukin-6Interleukin-8Matrix Metalloproteinase 3Quercetin

Identifiers

PMID37356505
PMCPMC10746834
OpenAlexW4381852728

What OpenQuestion holds

Textmetadata
LicenceTDM
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.