The Effect of IL-17A and Combined Mechanical Injury on Meniscal Tissue Integrity In Vitro
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jcm-14-07573.pdf
Description
Published version
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1.77 MB
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Checksum (MD5)
0d2d61be86612180aa1ed500070e1fc4
Author(s)
Ahrens, Greta
Gellhaus, Florian
Weitkamp, Jan-Tobias
Behrendt, Peter
Cossais, François
Rolauffs, Bernd
Grodzinsky, Alan J
Kurz, Bodo
Date Issued
October 24, 2025
Journal
Journal of Clinical Medicine
Publisher
Multidisciplinary Digital Publishing Institute
Citation
Ahrens, G., Gellhaus, F., Weitkamp, J.-T., Behrendt, P., Cossais, F., Rolauffs, B., Grodzinsky, A. J., & Kurz, B. (2025). The Effect of IL-17A and Combined Mechanical Injury on Meniscal Tissue Integrity In Vitro. Journal of Clinical Medicine, 14(21), 7573.
Version
Final published version
Abstract
Objectives: Meniscal integrity is crucial for knee joint stability and the prevention of osteoarthritis (OA) development. Recent studies suggested that mechanical overload and interleukin (IL)-17A may be important intertwined players in meniscal degeneration, but a direct impact of IL-17A on the meniscus has not been investigated. Therefore, the aim of this study was to analyze the effect of IL-17A on meniscal tissue with and without combined mechanical injury (MI). Methods: Meniscal explant disks (1 mm height, 3 mm diameter) were isolated from bovine menisci (preserving the native tibial superficial zone) and exposed to IL-17A [0–100 ng/mL] and/or MI (single compression, 50% strain, strain rate 1 mm/sec). After three days of incubation in a serum-free medium, the proteoglycan release (sGAG; DMMB assay), mRNA level of matrix-degrading enzymes (qRT-PCR), aggrecan degradation (NITEGE immunostaining), and cell death (histomorphometry of nuclear blebbing/apoptosis and condensed nuclei/unspecified cell death) were determined. Statistics: one- and two-way ANOVA with Tukey’s multiple comparisons or Kruskal– Wallis with post hoc testing. Results: IL-17A increased sGAG release in a dose-dependent significant manner. MI also induced the release of sGAG significantly, but the combination with IL-17A showed the highest levels. Both IL-17A and MI individually affected the mRNA levels for ADAMTS4 and MMP-13 slightly, but the combination of both particularly induced a significant increase in mRNA levels. Signals for the ADAMTS4-related aggrecan neoepitope NITEGE were elevated by IL-17A in superficial areas of the excised tissue and by MI in superficial and deeper areas. The combination of both stimuli intensified this signal further. MI increased the number of cells with condensed nuclei significantly and induced apoptosis in a small proportion of cells. IL-17A had no significant impact on the amount of condensed or apoptotic nuclei. Conclusions: Our findings emphasize an interaction between inflammatory cytokine IL-17A signaling and mechanical stress since IL17A induced matrix degeneration in meniscal tissue, which intensified in combination with a trauma. The latter might create a post-traumatic environment that promotes meniscal degeneration and subsequently osteoarthritis progression.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science
Massachusetts Institute of Technology. Department of Mechanical Engineering
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DOI of Published Version
https://doi.org/10.3390/jcm14217573
