Mitochondrial dysfunction and impaired osteogenic capacity define stress-induced osteoblast senescence
- 1University Ulm
Abstract
Cellular senescence has emerged as a key contributor to age-related skeletal deterioration; however, the defining characteristics of senescent osteoblasts remain incompletely understood, hindering efforts to identify the cellular mechanisms that drive age-associated bone loss and potential therapeutic targets. Here, we compared doxorubicin- and hydrogen peroxide-induced senescence and established a robust in vitro osteoblast model that enables the stable maintenance of stress-induced premature senescence. Doxorubicin-treated MC3T3-E1 cells exhibited persistent growth arrest, a pronounced senescence-associated secretory phenotype (SASP), and impaired osteogenic function accompanied by marked mitochondrial dysfunction, including reduced respiratory capacity and altered mitochondrial morphology. Transcriptomic comparison with aged murine bone revealed a partial overlap with in vivo aging-associated gene expression signatures, particularly among genes involved in extracellular matrix organization and skeletal development, supporting the physiological relevance of the model. Importantly, key features of senescence, including the senescence-associated mitochondrial phenotype and impaired osteogenic capacity, were recapitulated in primary human osteoblasts. Collectively, these findings establish a robust model of stress-induced osteoblast senescence and demonstrate that senescent osteoblasts exhibit mitochondrial dysfunction, impaired osteogenic capacity, and molecular features that resemble aspects of skeletal aging.
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BibTeX
@misc{frey2026mitochondrial,
title = {{Mitochondrial dysfunction and impaired osteogenic capacity define stress-induced osteoblast senescence}},
author = {T. Frey and H. Vogg and M. Ahmad and Y. Nakano and M. Vogel and S. Nungess and A. Schoppa and H. Geiger and A. Ignatius and J. Riegger},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.13.751251},
url = {https://www.biorxiv.org/content/10.64898/2026.09.13.751251v1},
note = {CC BY-NC},
}
RIS
TY - UNPB
TI - Mitochondrial dysfunction and impaired osteogenic capacity define stress-induced osteoblast senescence
AU - T. Frey
AU - H. Vogg
AU - M. Ahmad
AU - Y. Nakano
AU - M. Vogel
AU - S. Nungess
AU - A. Schoppa
AU - H. Geiger
AU - A. Ignatius
AU - J. Riegger
PY - 2026
DA - 2026/09/13
PB - bioRxiv
DO - 10.64898/2026.09.13.751251
UR - https://www.biorxiv.org/content/10.64898/2026.09.13.751251v1
AB - Cellular senescence has emerged as a key contributor to age-related skeletal deterioration; however, the defining characteristics of senescent osteoblasts remain incompletely understood, hindering efforts to identify the cellular mechanisms that drive age-associated bone loss and potential therapeutic targets. Here, we compared doxorubicin- and hydrogen peroxide-induced senescence and established a robust in vitro osteoblast model that enables the stable maintenance of stress-induced premature senescence. Doxorubicin-treated MC3T3-E1 cells exhibited persistent growth arrest, a pronounced senescence-associated secretory phenotype (SASP), and impaired osteogenic function accompanied by marked mitochondrial dysfunction, including reduced respiratory capacity and altered mitochondrial morphology. Transcriptomic comparison with aged murine bone revealed a partial overlap with in vivo aging-associated gene expression signatures, particularly among genes involved in extracellular matrix organization and skeletal development, supporting the physiological relevance of the model. Importantly, key features of senescence, including the senescence-associated mitochondrial phenotype and impaired osteogenic capacity, were recapitulated in primary human osteoblasts. Collectively, these findings establish a robust model of stress-induced osteoblast senescence and demonstrate that senescent osteoblasts exhibit mitochondrial dysfunction, impaired osteogenic capacity, and molecular features that resemble aspects of skeletal aging.
ER -