STING regulates aging-related osteoporosis by mediating the Hk2-Vdac1 mitochondrial axis.

Wenjin Cai, Jiaying Zhao, Yani Chen, Ning Gao, Bicong Gao, Zengzhe Liu, Tingben Huang, Lingling Dong, Guoli Yang, Ying Wang

Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China.Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Zhejiang Provincial Clinical Research Center for Oral Diseases, Key Laboratory of Oral Biomedical Research of Zhejiang Province, Cancer Center of Zhejiang University, Engineering Research Center of Oral Biomaterials and Devices of Zhejiang Province, Hangzhou, 310000, China. · pubmed

Paper

Abstract

Metabolic abnormalities and mild inflammation are hallmarks of aging and major driving factors for aging-related damage and bone metabolic diseases. Mitochondria are crucial links in energy metabolism and immune homeostasis regulation. Mitochondrial dysfunction is considered one of the pathogenic factors of aging-related osteoporosis, but its mechanism of action needs further research. Here, we demonstrated that the interaction between stimulator of interferon genes (STING)-mediated regulation of hexokinase 2 (Hk2)-voltage-dependent anion channel-1 (Vdac1) is a critical factor contributing to mitochondrial dysfunction and osteogenic abnormalities during aging. As the aging process progresses, factors related to aging cause an increase in STING expression, which disrupts the interaction between Hk2 and Vdac1. Dissociation of Hk2 from Vadc1 triggered the opening of the mitochondrial inner mitochondrial permeability transition pore (mPTP), leading to mitochondrial dysfunction and abnormal osteogenic differentiation, thereby disrupting bone homeostasis. In brief, this study demonstrates that STING acts as an intracellular metabolic Checkpoint, influencing mitochondrial function to promote the development of osteoporosis. These findings significantly enhance the development of STING-targeted treatments for aging-related osteoporosis.

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Research summary

The paper addresses the mechanisms underlying aging-related osteoporosis, specifically focusing on the role of STING in mitochondrial dysfunction and bone metabolic diseases. By exploring the interaction between STING, Hk2, and Vdac1, it contributes to understanding the biological processes that may underlie aging and age-related diseases. However, while the findings are solid and provide insights into potential therapeutic targets, they do not represent a major breakthrough or transformative advancement in the field of longevity research.

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