ArticlePloS one2015
Effects of Age and Estrogen on Skeletal Gene Expression in Humans as Assessed by RNA Sequencing.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02349113 (Effects of Acute Estrogen Therapy on Bone Formation), which is not on this map. Cited by 53 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.
Effects of Acute Estrogen Therapy on Bone Formation
Who cites it
53 citing papers in PubMed, 76 citations in OpenAlex.
- Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism.Nature communications · 2020Trial
- Sympathetic β1-adrenergic signaling contributes to regulation of human bone metabolism.The Journal of clinical investigation · 2018Trial
- Bone aging: a paradigm of multiscale degeneration and targeted rejuvenation.Bone research · 2026Review
- Effects of catecholamines on bone and mineral metabolism in patients with pheochromocytoma and paraganglioma.The Journal of clinical endocrinology and metabolism · 2026Review
- Mcu regulates bone formation via mitochondrial calcium uptake and lineage allocation.Experimental & molecular medicine · 2026Article
- Integrated single-cell multi-omics profiling reveals a senescence-associated hematopoietic landscape and regulatory network in aging bone marrow.Biogerontology · 2025Article
- SenolyticSynergy: An Attention-Based Network for Discovering Novel Senolytic Combinations via Human Aging Genomics.International journal of molecular sciences · 2025Article
- Developing a novel aging assessment model to uncover heterogeneity in organ aging and screening of aging-related drugs.Genome medicine · 2025Article
- Identification of protein-coding genes associated with metastatic prostate cancer.Endocrine-related cancer · 2025Article
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- Differential efficacy of two small molecule PHLPP inhibitors to promote nucleus Pulposus cell health.JOR spine · 2024Article
- Identification of the transcriptome signatures and immune-inflammatory responses in postmenopausal osteoporosis.Heliyon · 2024Article
- The impact of ageing mechanisms on musculoskeletal system diseases in the elderly.Frontiers in immunology · 2024Review
- Genetic and Gene Expression Resources for Osteoporosis and Bone Biology Research.Current osteoporosis reports · 2023Review
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- Cellular senescence in skeletal disease: mechanisms and treatment.Cellular & molecular biology letters · 2023Review
- Loss of Notch signaling in skeletal stem cells enhances bone formation with aging.Bone research · 2023Article
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- A new gene set identifies senescent cells and predicts senescence-associated pathways across tissues.Nature communications · 2022Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledPrecise delineation of the specific genes and pathways altered with aging and estrogen (E) therapy may lead to new skeletal biomarkers and the development of novel bone therapeutics. Previous human bone studies, however, have been limited by only examining pre-specified genes and pathways. High-throughput RNA sequencing (RNAseq), on the other hand, offers an unbiased approach to examine the entire transcriptome. Here we present an RNAseq analysis of human bone samples, obtained from iliac crest needle biopsies, to yield the first in vivo interrogation of all genes and pathways that may be altered in bone with aging and E therapy in humans. 58 healthy women were studied, including 19 young women (mean age ± SD, 30.3 ± 5.4 years), 19 old women (73.1 ± 6.6 years), and 20 old women treated with 3 weeks of E therapy (70.5 ± 5.2 years). Using generally accepted criteria (false discovery rate [q] < 0.10), aging altered a total of 678 genes and 12 pathways, including a subset known to regulate bone metabolism (e.g., Notch). Interestingly, the LEF1 transcription factor, which is a classical downstream target of the Wnt/β-catenin signaling pathway, was significantly downregulated in the bones from the old versus young women; consistent with this, LEF1 binding sites were significantly enriched in the promoter regions of the differentially expressed genes in the old versus young women, suggesting that aging was associated with alterations in Wnt signaling in bone. Further, of the 21 unique genes altered in bone by E therapy, the expression of INHBB (encoding for the inhibin, beta B polypeptide), which decreased with aging (by 0.6-fold), was restored to young adult levels in response to E therapy. In conclusion, our data demonstrate that aging alters a substantial portion of the skeletal transcriptome, whereas E therapy appears to have significant, albeit less wide-ranging effects. These data provide a valuable resource for the potential identification of novel biomarkers associated with age-related bone loss and also highlight potential pathways that could be targeted to treat osteoporosis.
trial registrationClinicalTrials.gov NCT02349113.
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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.