Exploring DNA methylation profiles in the pathogenesis of human osteoporosis via whole-genome bisulfite sequencing

作者：Yinyin Zhang, Yinyin Zhang, Guoying Wu, Jialu Hou, Yeling Zhong, Yukai Zhang, Yukai Zhang, Shishuo Xiong, Zehua Guo, Ying Li · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2026 · DOI：10.64898/2026.01.05.697801 · 研究领域：Epigenetics and DNA Methylation、Bone Metabolism and Diseases、Bone health and osteoporosis research

Abstract Background Osteoporosis is a prevalent bone metabolic disorder characterized by reduced bone mass, disruption of bone microarchitecture, and increased bone fragility, leading to a heightened risk of fracture. This condition significantly impairs patients’ quality of life and increases mortality risk. Emerging evidence suggests that DNA methylation may play a crucial role in regulating the expression of genes related to bone metabolism, thereby influencing the development of osteoporosis. However, the precise relationship between DNA methylation and osteoporosis remains unclear and warrants further investigation. Results Our study revealed significant differences in both the quantity and ratio of DNA methylation between individuals with osteoporosis and non-osteoporosis controls, with differences predominantly occurring in CpG islands. GO/KEGG enrichment analyses highlighted distinct osteoporosis-related gene pathways. Notably, we identified six genes, MSX1, HOXD4, AXIN2, WNT5A, TGFB1, and STAT3, respectively, that are potentially involved in the pathogenesis of osteoporosis and are broadly involved in various diseases and biological processes. Conclusions These findings indicate distinct methylation patterns between osteoporosis patients and healthy individuals, with differential methylation levels in genes associated with osteoporosis. This research offers new insights into the epigenetic mechanisms underlying osteoporosis.