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

Bone & Joint Research

article

Tae Jun Park¹  Seung Yeon Park¹  Wonjun Cho¹  Heeseung Oh¹  Hyun Jung Lee²  A. M. Abd El-Aty³  Cemil Bayram⁴  Ji Hoon Jeong¹  Tae Woo Jung¹ 

[1] Department of Pharmacology, College of Medicine, Chung-Ang University;Department of Global Innovative Drugs, Graduate School of Chung-Ang University;Department of Pharmacology, Faculty of Veterinary Medicine, Cairo University;Department of Medical Pharmacology, Medical Faculty, Ataturk University

关键词: DEL-1;    ER stress;    Apoptosis;    AMPK;    Autophagy;    Tenocytes;    inflammation;    apoptosis;    autophagy;    Western blotting;    caspase 3;    Obesity;    insulin;    staining;    tendinitis;    RNA;   

DOI  :  10.1302/2046-3758.1112.BJR-2022-0077.R2

学科分类：骨科学

来源: British Editorial Society Of Bone And Joint Surgery

【 摘 要 】

AimsMyokine developmental endothelial locus-1 (DEL-1) has been documented to alleviate inflammation 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.MethodsHuman primary tenocytes were cultured in palmitate (400 μM) and palmitate plus DEL-1 (0 to 2 μg/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 viability assay and caspase 3 activity assay.ResultsWe found that treatment with DEL-1 suppressed palmitate-induced inflammation, ER stress, and apoptosis in human primary tenocytes. DEL-1 treatment augmented LC3 conversion and p62 degradation as well as AMPK phosphorylation. Moreover, small interfering RNA for AMPK or 3-methyladenine (3-MA), an autophagy inhibitor, abolished the suppressive 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.ConclusionThese results revealed that DEL-1 suppresses inflammation and ER stress, thereby attenuating tenocyte apoptosis through AMPK/autophagy-mediated signalling. Thus, regular exercise or administration of DEL-1 may directly contribute to improving tendinitis exacerbated by obesity and insulin resistance.

【 授权许可】

CC BY-NC