(W1215) ADIPONECTIN KNOCKOUT UNVEILED IMPAIRED CELL FATE AND SURVIVAL IN TENDON-DERIVED STEM/PROGENITOR CELLS: INSIGHTS INTO THE PATHOGENESIS OF CHRONIC TENDINOPATHY

Abstract: Chronic tendinopathy is characterized by excessive inflammation and erroneous differentiation of tendon-derived stem/progenitor cells (TDSCs), resulting in a reduced pool of TDSCs available for tendon regeneration. It presents a significant challenge in sports medicine, with limited effective treatment options due to its unclear etiopathogenesis. Adiponectin, a hormone-like factor, exhibits anti-inflammatory, anti-apoptotic, and tissue regenerative properties across various cell types, including macrophages and endothelial cells. Our unpublished data revealed an increased adiponectin expression in both clinical samples and animal model of tendinopathy, implying a potential role of adiponectin in the disease pathogenesis. However, whether it exerts protective or detrimental effects in tendons remains unclear. This study aimed to explore the effects of adiponectin knockout on the cell fate and survival of TDSCs. TDSCs were isolated from wild-type or adiponectin knockout mice. Gene expression of tenogenic and non-tenogenic markers was analyzed, while clonogenicity, apoptosis, viability, and migratory properties were assessed to understand the effects of adiponectin deficiency on stem cell characteristics. This study uncovered key changes in adiponectin knockout TDSCs, including a significant decrease in the gene expression of tenogenic markers and an increase in non-teno genic markers, signaling a shift away from the desired tenogenic lineage. Clonogenicity assay revealed highly reduced colony formation, indicating impaired self-renewal potential, while increased apoptosis suggested disrupted survival mechanisms. Viability assessment showed a significant decrease in cell viability in the absence of adiponectin, and functional studies unveiled reduced migration capability, as evidenced in wound healing and transwell assays. These findings highlight the significant negative impacts of adiponectin knockout on the fate, survival, and function of TDSCs. The upregulation of adiponectin in the clinical samples and animal model of tendinopathy may thus be an attempt to enhance TDSC functions and promote tendon repair. Future studies should test the effects of adiponectin supplementation on TDSCs and tendons, as it may serve as a potential target for treating chronic tendinopathy.

Funding Source: This study was supported by the Research Grants Council (Ref. 14111624) and Health@InnoHK (Ref. ITC RC/IHK/4/7).

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