@article{Li2025, 
author = {Pan Li and Chao Zheng and Jingyan Hu and Weiguang Lu and Dong Wang and Xue Hao and Chengxiang Zhao and Liu Yang and Zhuojing Luo and Qiang Jie},
title = {Melatonin ameliorates Slc26a2-associated chondrodysplasias by attenuating endoplasmic reticulum stress and apoptosis of chondrocytes},
year = {2025},
journal = {Genes & Diseases},
volume = {12},
number = {2},
pages = {101350},
keywords = {Ca2+overload, Chondrodysplasia, Endoplasmic reticulum stress, Melatonin, SLC26A2},
url = {https://www.sciopen.com/article/10.1016/j.gendis.2024.101350},
doi = {10.1016/j.gendis.2024.101350},
abstract = {Although the pathogenesis and mechanism of congenital skeletal dysplasia are better understood, progress in drug development and intervention research remains limited. Here we report that melatonin treatment elicits a mitigating effect on skeletal abnormalities caused by SLC26A2 deficiency. In addition to our previous finding of endoplasmic reticulum stress upon SLC26A2 deficiency, we found calcium (Ca2+) overload jointly contributed to SLC26A2-associated chondrodysplasias. Continuous endoplasmic reticulum stress and cytosolic Ca2+ overload in turn triggered apoptosis of growth plate chondrocytes. Melatonin, known for its anti-oxidant and anti-inflammatory properties, emerged as a promising therapeutic approach in our study, which enhanced survival, proliferation, and maturation of chondrocytes by attenuating endoplasmic reticulum stress and Ca2+ overload. Our findings not only demonstrated the efficacy of melatonin in ameliorating abnormal function and cell fate of SLC26A2-deficient chondrocytes in vitro but also underscored its role in partially alleviating the skeletal dysplasia seen in Col2a1-CreERT2; Slc26a2fl/fl mice. As revealed by histology and micro-CT analyses, melatonin significantly improved retarded cartilage growth, defective trabecular bone formation, and tibial genu varum in vivo. Collectively, these data shed translational insights for drug development and support melatonin as a potential treatment for SLC26A2-related chondrodysplasias.}
}