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• W3195335445 abstract "Abstract Background Failing of intrinsic chondrocyte repair after mechanical stress is known as one of the most important initiators of osteoarthritis. Nonetheless, insight into these early mechano-pathophysiological processes in age-related human articular cartilage is still lacking. Such insights are needed to advance clinical development. To highlight important molecular processes of osteoarthritis mechano-pathology, the transcriptome-wide changes following injurious mechanical stress on human aged osteochondral explants were characterized. Methods Following mechanical stress at a strain of 65% (65%MS) on human osteochondral explants ( n 65%MS = 14 versus n control = 14), RNA sequencing was performed. Differential expression analysis between control and 65%MS was performed to determine mechanical stress-specific changes. Enrichment for pathways and protein-protein interactions was analyzed with Enrichr and STRING. Results We identified 156 genes significantly differentially expressed between control and 65%MS human osteochondral explants. Of note, IGFBP5 (FC = 6.01; FDR = 7.81 × 10 −3 ) and MMP13 (FC = 5.19; FDR = 4.84 × 10 −2 ) were the highest upregulated genes, while IGFBP6 (FC = 0.19; FDR = 3.07 × 10 −4 ) was the most downregulated gene. Protein-protein interactions were significantly higher than expected by chance ( P = 1.44 × 10 −15 with connections between 116 out of 156 genes). Pathway analysis showed, among others, enrichment for cellular senescence, insulin-like growth factor (IGF) I and II binding, and focal adhesion. Conclusions Our results faithfully represent transcriptomic wide consequences of mechanical stress in human aged articular cartilage with MMP13 , IGF binding proteins, and cellular senescence as the most notable results. Acquired knowledge on the as such identified initial, osteoarthritis-related, detrimental responses of chondrocytes may eventually contribute to the development of effective disease-modifying osteoarthritis treatments." @default.
• W3195335445 created "2021-08-30" @default.
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• W3195335445 date "2021-08-16" @default.
• W3195335445 modified "2023-10-06" @default.
• W3195335445 title "Elucidating mechano-pathology of osteoarthritis: transcriptome-wide differences in mechanically stressed aged human cartilage explants" @default.
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• W3195335445 doi "https://doi.org/10.1186/s13075-021-02595-8" @default.
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