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Molecular treatments to reduce catabolic effects in human meniscus explant models

Sjögren, Amanda LU orcid ; Lindblom, Karin LU ; Turkiewicz, Aleksandra LU ; Englund, Martin LU orcid and Önnerfjord, Patrik LU orcid (2025) In Osteoarthritis and Cartilage Open 7(3).
Abstract

Objectives: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 ​+ ​interleukin-6 receptor ​+ ​tumor necrosis factor alpha (IL6/TNF) and oncostatin M ​+ ​tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone (DEX), ii) a Link-N peptide (Link-N) and iii) a peptide from chondroadherin (CKF). Design: Healthy lateral menisci from deceased donors (n ​= ​6; age ​= ​25–70 years, 4 males, 2 females), were sliced and randomized for experimental groups (combinations of the catabolic models and anti-catabolic treatments) and a control group. Culture media were analyzed, every third day until day 18, by mass spectrometry-based proteomics. Linear mixed... (More)

Objectives: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 ​+ ​interleukin-6 receptor ​+ ​tumor necrosis factor alpha (IL6/TNF) and oncostatin M ​+ ​tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone (DEX), ii) a Link-N peptide (Link-N) and iii) a peptide from chondroadherin (CKF). Design: Healthy lateral menisci from deceased donors (n ​= ​6; age ​= ​25–70 years, 4 males, 2 females), were sliced and randomized for experimental groups (combinations of the catabolic models and anti-catabolic treatments) and a control group. Culture media were analyzed, every third day until day 18, by mass spectrometry-based proteomics. Linear mixed effect models were used to estimate differences in protein abundances between groups. Results: A total of 662 proteins were identified in all menisci. Cytokine-treated meniscus explant models showed increased release of osteoarthritis-related proteins such as matrix metalloproteinases (MMPs). For example, MMP1: IL6/TNF vs. ctrl; log2 fold-change 2.2 95 ​% confidence interval [1.8, 2.5] and OSM/TNF vs. ctrl; log2 fold-change 2.8 [2.4, 3.1]. There was no treatment effect in explant meniscus with the addition of either Link-N or CKF. Treatment effects were, however, evident with the addition of DEX. For example, MMP1: IL6/TNF ​+ ​DEX vs. ctrl; log2 fold-change −1.8 [-2.2, −1.4] and OSM/TNF ​+ ​DEX vs. ctrl; log2 fold-change −0.3 [-0.7, 0.04]. Conclusion: We confirmed that both catabolic models induce changes in osteoarthritis-related proteins. DEX treatment is effective in mitigating the catabolic response in meniscus explant models and may be further explored for its effects in the treatment of meniscus degeneration.

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author
; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Explant model, Human tissue, Meniscus, Osteoarthritis, Proteomics
in
Osteoarthritis and Cartilage Open
volume
7
issue
3
article number
100618
publisher
Elsevier
external identifiers
  • scopus:105004401934
ISSN
2665-9131
DOI
10.1016/j.ocarto.2025.100618
language
English
LU publication?
yes
id
deb60e15-c579-4fd0-b328-c96e9227f257
date added to LUP
2025-07-17 09:56:44
date last changed
2025-07-17 09:57:30
@article{deb60e15-c579-4fd0-b328-c96e9227f257,
  abstract     = {{<p>Objectives: 1. To validate catabolic meniscus explant models induced by cytokines: interleukin-6 ​+ ​interleukin-6 receptor ​+ ​tumor necrosis factor alpha (IL6/TNF) and oncostatin M ​+ ​tumor necrosis factor alpha (OSM/TNF). 2. To evaluate three potential anti-catabolic treatments: i) dexamethasone (DEX), ii) a Link-N peptide (Link-N) and iii) a peptide from chondroadherin (CKF). Design: Healthy lateral menisci from deceased donors (n ​= ​6; age ​= ​25–70 years, 4 males, 2 females), were sliced and randomized for experimental groups (combinations of the catabolic models and anti-catabolic treatments) and a control group. Culture media were analyzed, every third day until day 18, by mass spectrometry-based proteomics. Linear mixed effect models were used to estimate differences in protein abundances between groups. Results: A total of 662 proteins were identified in all menisci. Cytokine-treated meniscus explant models showed increased release of osteoarthritis-related proteins such as matrix metalloproteinases (MMPs). For example, MMP1: IL6/TNF vs. ctrl; log2 fold-change 2.2 95 ​% confidence interval [1.8, 2.5] and OSM/TNF vs. ctrl; log2 fold-change 2.8 [2.4, 3.1]. There was no treatment effect in explant meniscus with the addition of either Link-N or CKF. Treatment effects were, however, evident with the addition of DEX. For example, MMP1: IL6/TNF ​+ ​DEX vs. ctrl; log2 fold-change −1.8 [-2.2, −1.4] and OSM/TNF ​+ ​DEX vs. ctrl; log2 fold-change −0.3 [-0.7, 0.04]. Conclusion: We confirmed that both catabolic models induce changes in osteoarthritis-related proteins. DEX treatment is effective in mitigating the catabolic response in meniscus explant models and may be further explored for its effects in the treatment of meniscus degeneration.</p>}},
  author       = {{Sjögren, Amanda and Lindblom, Karin and Turkiewicz, Aleksandra and Englund, Martin and Önnerfjord, Patrik}},
  issn         = {{2665-9131}},
  keywords     = {{Explant model; Human tissue; Meniscus; Osteoarthritis; Proteomics}},
  language     = {{eng}},
  number       = {{3}},
  publisher    = {{Elsevier}},
  series       = {{Osteoarthritis and Cartilage Open}},
  title        = {{Molecular treatments to reduce catabolic effects in human meniscus explant models}},
  url          = {{http://dx.doi.org/10.1016/j.ocarto.2025.100618}},
  doi          = {{10.1016/j.ocarto.2025.100618}},
  volume       = {{7}},
  year         = {{2025}},
}