Oxygen Sensing in Osteocytes: From Physiology to Age-related Osteoporosis.
Document Type
Article
Publication Date
6-21-2025
Original Citation
Janeczko K,
Agoro R.
Oxygen Sensing in Osteocytes: From Physiology to Age-related Osteoporosis. Curr Osteoporos Rep. 2025;23(1):28. Epub 20250621.
Keywords
JMG, Osteocytes, Humans, Osteoporosis, Oxygen, Aging, Fibroblast Growth Factor-23, Adaptor Proteins, Signal Transducing, Animals, Fibroblast Growth Factors, RANK Ligand, Bone Morphogenetic Proteins, Membrane Glycoproteins, Bone and Bones, Genetic Markers
JAX Source
Curr Osteoporos Rep. 2025;23(1):28. Epub 20250621.
ISSN
1544-2241
PMID
40542900
DOI
https://doi.org/10.1007/s11914-025-00920-7
Abstract
PURPOSE OF THE REVIEW: The purpose of this review article is to discuss how oxygen sensing mechanisms regulate the expression of key osteocyte markers such as podoplanin (E11), sclerostin (SOST), receptor activator of nuclear factor-κB ligand (RANKL), and fibroblast growth factor 23 (FGF23); summarize the relevance of targeting oxygen sensing pathways in osteocytes to improve bone health; and highlight the importance of osteocyte oxygen sensing mechanisms in maintaining good bone health during aging.
RECENT FINDINGS: Oxygen sensing in osteocytes regulates osteocyte dendrites formation, bone mass and mineral metabolism through the regulation of E11, SOST, RANKL, and FGF23. Hypoxia Induced Factor (HIF) stabilization in osteocytes increases the activity of the histone deacetylase SIRT1 which represses SOST expression and increases the expression of FGF23. These recent findings suggest that targeting oxygen-associated pathways can be leveraged to control osteo-anabolic response and mineral metabolism. Aging is associated with the increase of circulating SOST; therefore, the mechanisms associated with SOST overproduction in bone may be linked to age-related changes in oxygen sensing in osteocytes. Understanding the changes of oxygen sensing mechanisms in osteocytes during aging may offer a therapeutic avenue to control SOST overproduction, a negative regulator of bone formation and therefore prevent age-related bone loss. We discuss how oxygen-sensing controls osteocyte physiology and how aging-mediated dysregulation of oxygen bioavailability promotes osteoporosis. We also explore how oxygen-modulating therapies can be used to improve bone healthspan.