Uncovering the cellular and molecular changes in tendon stem/progenitor cells attributed to tendon aging and degeneration.
Bottom Line: Comparing TSPC derived from young/healthy (Y-TSPC) and aged/degenerated human Achilles tendon biopsies (A-TSPC), we observed that A-TSPC exhibit a profound self-renewal and clonogenic deficits, while their multipotency was still retained.Time-lapse analysis showed that A-TSPC exhibit decelerated motion and delayed wound closure concomitant to a higher actin stress fiber content and a slower turnover of actin filaments.Lastly, based on the expression analyses of microarray candidates, we suggest that dysregulated cell-matrix interactions and the ROCK kinase pathway might be key players in TSPC aging.
Affiliation: Department of Surgery, Experimental Surgery and Regenerative Medicine, Ludwig Maximilians University Munich, Nussbaumstr. 20, 80336, Munich, Germany.Show MeSH
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Mentions: To identify molecular factors involved in tendon aging and degeneration, we performed microchip hybridization with RNA from three different donors per group. Comparative microarray analysis is summarized in a Venn diagram in Fig.2A, and the top 40 and 100 probesets are depicted in heatmaps in Fig.2B and Fig. S4, respectively (complete microarray data in Table S4). To identify a molecular pattern behind the observed transcriptomal shift, we performed gene ontology (GO) analysis with all differentially expressed probesets. In Fig.2C, exemplary entries from the ‘cellular component’ and ‘biological process’ gene clusters are shown. Finally, to spot the most relevant genes, we applied literature-based annotation approach as follows: using probesets with 2-fold changes, 130 known genes were identified and subjected to literature screening. Our investigation demonstrated that these genes distributed majorly in the following categories: (i) ‘cell–cell contact’, (ii) ‘cell adhesion’, (iii) ‘motility’, (iv) ‘migration’, (v) ‘cytoskeleton’, and (vi) ‘actin-related transcripts’ (Fig.2D and Table S5).
Affiliation: Department of Surgery, Experimental Surgery and Regenerative Medicine, Ludwig Maximilians University Munich, Nussbaumstr. 20, 80336, Munich, Germany.