Sialin-STAT3 axis regulates bone homeostasis in mice.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 41663362.
- Also identified by DOI 10.1038/s41413-025-00504-2 and PMC identifier 12887030.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
Mitochondrial regulation in mesenchymal stem cells (MSCs) serves as a critical determinant of bone formation and skeletal homeostasis. While dietary nitrate and its transporter Sialin are implicated in systemic homeostasis, their specific roles in MSCs' function remain unclear. Here, we demonstrate that Sialin deficiency impairs MSCs' function and disrupts bone homeostasis. Gain- and loss-of-function studies reveal that Sialin localizes to the mitochondrial membrane and promotes osteogenic differentiation by maintaining mitochondrial bioenergetic integrity. Mechanistically, Sialin recruits pSTAT3<sup>S727</sup> to mitochondria, forming a functional complex that activates mitochondrial bioenergy and stabilizes bone remodeling. Notably, dietary nitrate restores Sialin expression in aged mice, thereby enhancing MSCs' function and preventing osteoporosis. Our findings identify a nutrient-responsive signaling axis-nitrate-Sialin-pSTAT3<sup>S727</sup>-that promotes osteogenic differentiation via mitochondrial homeostasis, offering a potential therapeutic strategy for age-related osteoporosis.
Medical subject headings
- Homeostasis
- STAT3 Transcription Factor
- Bone and Bones