Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

Li, Kaihu; Zhang, Penghui; Zhu, Yong; Alini, Mauro; Grad, Sibylle; Li, Zhen

doi:10.3389/fbioe.2021.787020

Cited by 5 publications

(1 citation statement)

References 34 publications

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“…A previous study demonstrated that the addition of in ammatory cytokines IL-1β and TNF-α for 7 days to human osteochondral plugs could induce osteoarthritic characteristics ex vivo [19]. Human cartilage is a superior model for investigating the response of cartilage in joint diseases compared to bovine cartilage.…”

Section: Discussionmentioning

confidence: 99%

Establishment of an Ex Vivo Cartilage Degeneration Model by Combined Collagenase and Aggrecanase Treatment and Mechanical Loading

Wen,

Grad,

Creemers

et al. 2024

Preprint

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Background There is a substantial need for ex vivo cartilage degeneration models to assess new emerging cartilage repair strategies. Ex vivo cartilage explant models have the advantages of achieving standardized and reproducible experimental conditions while maintaining the cells in their native tissue environment. This study aimed to establish a bovine cartilage degeneration model to evaluate the safety and efficacy of novel cartilage repair therapies. Methods Bovine osteochondral plugs underwent a brief 5-minutes treatment with collagenase to induce mild cartilage degeneration by disrupting the collagen network. To induce a moderate cartilage degeneration, aggrecanase 1 and aggrecanase 2 were additionally applied to the cartilage for 40 minutes post-collagenase treatment to degrade aggrecan. Results Observations revealed sulphated glycosaminoglycan loss using both Collagenase Treatment and Collagenase and Aggrecanase Treatment, while chondrocyte viability was maintained. Both treatments resulted in acute inflammation during the initial two days, evidenced by elevated release of IL6 and nitric oxide. Collagenase treatment also increased Neo epitopes of aggrecan compared to the untreated plugs at day 7, suggesting endogenous aggrecanase activation by chondrocytes upon collagen network disruption. The additional effect of mechanical loading on cartilage degeneration was also explored. Mildly degenerated cartilage treated solely with collagenase could withstand 1 hour per day of cyclical load, at 10%-20% compression of cartilage thickness combined with interfacial shear. However, higher compression levels (20%-40% of cartilage thickness) with the same shear stress regimen led to necrosis of surface layer chondrocytes. Conclusions This study establishes a useful model for evaluating cartilage repair strategies, and screening anti-catabolic drugs, particularly overload-related osteoarthritis. Combining mild cartilage degeneration with mechanical loading can simulate different degrees of cartilage degeneration and hold potential as a valuable tool in preclinical research.

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Section: Discussionmentioning

confidence: 99%

Establishment of an Ex Vivo Cartilage Degeneration Model by Combined Collagenase and Aggrecanase Treatment and Mechanical Loading

Wen,

Grad,

Creemers

et al. 2024

Preprint

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Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model

Dechêne

Colin

Demazy

et al. 2022

Stem Cell Rev and Rep

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Background Osteoarthritis (OA) is a highly prevalent joint degenerative disease for which therapeutic treatments are limited or invasive. Cell therapy based on mesenchymal stem/stromal cells (MSCs) is therefore seen as a promising approach for this disease, in both human and horses. As the regenerative potential of MSCs is mainly conferred by paracrine function, the goal of this study was to characterize the secreted proteins of muscle-derived MSCs (mdMSCs) in an in vitro model of OA to evaluate the putative clinical interest of mdMSCs as cell therapy for joint diseases like osteoarthritis. Methods An equine osteoarthritis model composed of cartilage explants exposed to pro-inflammatory cytokines was first developed. Then, the effects of mdMSC co-culture on cartilage explant were studied by measuring the glycosaminoglycan release and the NO2− production. To identify the underlying molecular actors, stable isotope-labeling by amino acids in cell culture based secreted protein analyses were conducted, in the presence of serum. The relative abundance of highly sequenced proteins was finally confirmed by western blot. Results Co-culture with muscle-derived MSCs decreases the cytokine-induced glycosaminoglycan release by cartilage explants, suggesting a protecting effect of mdMSCs. Among the 52 equine proteins sequenced in the co-culture conditioned medium, the abundance of decorin and matrix metalloproteinase 3 was significantly modified, as confirmed by western blot analyses. Conclusions These results suggest that muscle-derived MSCs could reduce the catabolic effect of TNFα and IL-1β on cartilage explant by decreasing the secretion and activity of matrix metalloproteinase 3 and increasing the decorin secretion. Graphical abstract mdMSCs capacity to reduce the catabolic consequences of cartilage exposure to pro-inflammatory cytokines. These effects can be explained by mdMSC-secreted bioactive such as TIMP-1 and decorin, known as an inhibitor of MMP3 and an anti-inflammatory protein, respectively.

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Animal Models of Osteoarthritis: Updated Models and Outcome Measures 2016–2023

Chapman

Ghosh

Attari

et al. 2023

Regen. Eng. Transl. Med.

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Establishment of an Ex Vivo Inflammatory Osteoarthritis Model With Human Osteochondral Explants

Cited by 5 publications

References 34 publications

Establishment of an Ex Vivo Cartilage Degeneration Model by Combined Collagenase and Aggrecanase Treatment and Mechanical Loading

Establishment of an Ex Vivo Cartilage Degeneration Model by Combined Collagenase and Aggrecanase Treatment and Mechanical Loading

Characterization of the Proteins Secreted by Equine Muscle-Derived Mesenchymal Stem Cells Exposed to Cartilage Explants in Osteoarthritis Model

Animal Models of Osteoarthritis: Updated Models and Outcome Measures 2016–2023

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