ArticleOncotarget2016
Circadian factors BMAL1 and RORα control HIF-1α transcriptional activity in nucleus pulposus cells: implications in maintenance of intervertebral disc health.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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.
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Who cites it
37 citing papers in PubMed, 50 citations in OpenAlex.
- The role of sleep and circadian rhythms in intervertebral disc degeneration.European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society · 2026Review
- Review
- Loss of MCT1 mediated lactate uptake causes delayed endplate maturation and intervertebral disc degeneration.Cell death & disease · 2026Article
- HIF-1α and BMAL1 in bone regeneration: crosstalk between hypoxia response and circadian rhythm.Bone research · 2026Review
- Circadian regulation in intervertebral disc degeneration: mechanisms and clinical implications.Frontiers in molecular biosciences · 2026Review
- The Fluidic Connectome in Brain Disease: Integrating Aquaporin-4 Polarity with Multisystem Pathways in Neurodegeneration.International journal of molecular sciences · 2025Review
- Association ofInternational journal of molecular sciences · 2025Article
- Dialogue Between the Clock Gene Bmal1 and Retinopathy: What Is the Exact Relationship?CNS neuroscience & therapeutics · 2025Review
- Circadian gene BMAL1 ameliorates renal ischaemia-reperfusion injury in diabetic mice by enhancing mitophagy via the HIF-1/BNIP3 pathway.Scientific reports · 2025Article
- Control of circadian muscle glucose metabolism through the BMAL1-HIF axis in obesity.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- BMAL1 attenuates intervertebral disc degeneration by activating the SIRT1/PGC-1α pathway: evidence from vitro studies.Scientific reports · 2025Article
- Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review.Bone research · 2025Review
- Role of circadian clock in female embryo implantation.Frontiers in cell and developmental biology · 2025Review
- Chronotherapy and intervertebral disc degeneration: understanding the role of circadian rhythm in degenerative processes.Frontiers in cell and developmental biology · 2025Review
- Review
- Article
- Regulation of protein O-GlcNAcylation by circadian, metabolic, and cellular signals.The Journal of biological chemistry · 2024Review
- A new perspective on intervertebral disc calcification-from bench to bedside.Bone research · 2024Review
- Increased HIF-2α activity in the nucleus pulposus causes intervertebral disc degeneration in the aging mouse spine.Frontiers in cell and developmental biology · 2024Article
- The contribution of circadian clock to the biological processes.Frontiers in molecular biosciences · 2024Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
BMAL1 and RORα are major regulators of the circadian molecular oscillator. Since previous work in other cell types has shown cross talk between circadian rhythm genes and hypoxic signaling, we investigated the role of BMAL1 and RORα in controlling HIF-1-dependent transcriptional responses in NP cells that exist in the physiologically hypoxic intervertebral disc. HIF-1-dependent HRE reporter activity was further promoted by co-transfection with either BMAL1 or RORα. In addition, stable silencing of BMAL1 or inhibition of RORα activity resulted in decreased HRE activation. Inhibition of RORα also modulated HIF1α-TAD activity. Interestingly, immunoprecipitation studies showed no evidence of BMAL1, CLOCK or RORα binding to HIF-1α in NP cells. Noteworthy, stable silencing of BMAL1 as well as inhibition of RORα decreased expression of select HIF-1 target genes including VEGF, PFKFB3 and Eno1. To delineate if BMAL1 plays a role in maintenance of disc health, we studied the spinal phenotype of BMAL1-null mice. The lumbar discs of null mice evidenced decreased height, and several parameters associated with vertebral trabecular bone quality were also affected in nulls. In addition, null animals showed a higher ratio of cells to matrix in NP tissue and hyperplasia of the annulus fibrosus. Taken together, our results indicate that BMAL1 and RORα form a regulatory loop in the NP and control HIF-1 activity without direct interaction. Importantly, activities of these circadian rhythm molecules may play a role in the adaptation of NP cells to their unique niche.
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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.