Developmental endothelial locus-1 attenuates palmitate- induced apoptosis in tenocytes through the AMPK/autophagy-mediated suppression of inflammation and endoplasmic reticulum stress

Aims Myokine developmental endothelial locus -1 (DEL -1) has been documented to alleviate in-flammation and endoplasmic reticulum (ER) stress in various cell types. However, the effects of DEL -1 on inflammation, ER stress, and apoptosis in tenocytes remain unclear. Methods Human primary tenocytes were cultured in palmitate (400 mu M) and palmitate plus DEL -1 (0 to 2 mu g/ml) conditions for 24 hours. The expression levels of ER stress markers and cleaved caspase 3, as well as phosphorylated 5' adenosine monophosphate-activated protein kinase (AMPK) and autophagy markers, were assessed by Western blotting. Autophagosome formation was measured by staining with monodansylcadaverine, and apoptosis was determined by cell via-bility assay and caspase 3 activity assay.Results We found that treatment with DEL -1 suppressed palmitate-induced inflammation, ER stress, and apoptosis in human primary tenocytes. DEL -1 treatment augmented LC3 con-version and p62 degradation as well as AMPK phosphorylation. Moreover, small interfer-ing RNA for AMPK or 3-methyladenine (3 -MA), an autophagy inhibitor, abolished the sup-pressive effects of DEL -1 on inflammation, ER stress, and apoptosis in tenocytes. Similar to DEL -1, 5- aminoimidazole- 4-carboxamide ribonucleotide (AICAR), an activator of AMPK, also attenuated palmitate-induced inflammation, ER stress, and apoptosis in tenocytes, which 3 -MA reversed.Conclusion These results revealed that DEL -1 suppresses inflammation and ER stress, thereby atten-uating tenocyte apoptosis through AMPK/autophagy-mediated signalling. Thus, regular exercise or administration of DEL -1 may directly contribute to improving tendinitis exac-erbated by obesity and insulin resistance.

Automated summary

This study reveals that DEL-1 can suppress inflammation and ER stress in tenocytes, thereby attenuating tenocyte apoptosis through AMPK/autophagy-mediated signaling.