ArticleBiology2025
Mechanistic Study of Hypoxia-Mediated Regulation of Osteoblast Senescence via ATP6V1A-Dependent Modulation of Metabolic Remodeling.
Article in Biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors.
Funding
Abstract
backgroundOsteoblast senescence constitutes one of the major mechanisms in bone degeneration and is under tight regulation by metabolism and oxidative stress. While hypoxia has recently emerged as an important microenvironmental factor influencing the function of bone cells, its role in osteoblast senescence and metabolic regulation has yet to be defined.
methodsThe present work entails hypoxia-modulated osteoblast senescence at one level, transcriptomic and metabolomic sequencing, and two levels, in vitro MC3T3-E1 and in vivo AAV-shAtp6v1a mouse models. In transcriptome profiling, hypoxia-responsive genes were identified, whereas non-targeted metabolomics was used to uncover metabolic alterations induced by ATP6V1A knockdown. Oxidative stress and mitochondrial function were assessed by qRT-PCR, Western blotting, SA-β-Gal staining, ROS detection, JC-1 mitochondrial potential, and immunofluorescence. Micro-CT, H&E, Masson, and immunohistochemistry studies were performed to investigate bone structure and protein expression in vivo.
resultsHypoxia markedly mitigated osteoblast senescence, decreasing p53 and p21 expressions and the number of SA-β-Gal-positive cells. It reduced intracellular ROS levels and increased HK2 and LDH expression, decreased ATP, and increased lactate, hinting at a shift toward glycolysis. Transcriptome analysis identified ATP6V1A as one of the major hypoxia-downregulated genes. Knockdown of ATP6V1A reduced ROS levels, inhibited p21 expression, improved mitochondrial function. Metabolomics disclosed remapping pathways in glycolysis, lipid, and amino acid metabolism.
conclusionsThis study identifies a "Hypoxia-ATP6V1A-Oxidative Stress-Metabolic Remodeling-Anti-Senescence" axis, demonstrating that hypoxia delays osteoblast senescence by downregulating ATP6V1A, suppressing oxidative stress, and reprogramming metabolism, providing new insights and potential therapeutic targets for bone degenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.