ArticleThe Journal of biological chemistry2014
α1-adrenergic receptor signaling in osteoblasts regulates clock genes and bone morphogenetic protein 4 expression through up-regulation of the transcriptional factor nuclear factor IL-3 (Nfil3)/E4 promoter-binding protein 4 (E4BP4).
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Osteoporosis and Skeletal Fragility in non-Metastatic Pheochromocytomas and Paragangliomas: The Adrenergic-Skeletal Axis.Calcified tissue international · 2026Review
- Differential Effects of Psychogenic Stress on Bone Morphology and Metabolism in Wistar Rats.Journal of bone metabolism · 2026Article
- Sympathetic regulation of bone homeostasis and remodeling: molecular mechanisms, pathophysiological roles, and therapeutic implications.Frontiers in immunology · 2026Review
- Review
- The function of GPCRs in different bone cells.International journal of biological sciences · 2025Review
- The specificities, influencing factors, and medical implications of bone circadian rhythms.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Review
- A wrinkle in time: circadian biology in pulmonary vascular health and disease.American journal of physiology. Lung cellular and molecular physiology · 2022Article
- Orexin-A Reverse Bone Mass Loss Induced by Chronic Intermittent Hypoxia Through OX1R-Nrf2/HIF-1α Pathway.Drug design, development and therapy · 2022Article
- Sympathetic activity in breast cancer and metastasis: partners in crime.Bone research · 2021Review
- Icariin promotes osteogenic differentiation of BMSCs by upregulating BMAL1 expression via BMP signaling.Molecular medicine reports · 2020Article
- Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes.BMC genomics · 2018Article
- Hypophosphatemia Regulates Molecular Mechanisms of Circadian Rhythm.Scientific reports · 2018Article
- Insights into the Role of Circadian Rhythms in Bone Metabolism: A Promising Intervention Target?BioMed research international · 2018Review
- Global Disruption of α2A Adrenoceptor Barely Affects Bone Tissue but Minimizes the Detrimental Effects of Thyrotoxicosis on Cortical Bone.Frontiers in endocrinology · 2018Article
- Regulation of Clock Genes by Adrenergic Receptor Signaling in Osteoblasts.Neurochemical research · 2018Review
- Heterogeneous nuclear ribonucleoprotein A1 regulates rhythmic synthesis of mouse Nfil3 protein via IRES-mediated translation.Scientific reports · 2017Article
- α1B -Adrenoceptor signalling regulates bone formation through the up-regulation of CCAAT/enhancer-binding protein δ expression in osteoblasts.British journal of pharmacology · 2016Article
- α1B-Adrenergic receptor signaling controls circadian expression of Tnfrsf11b by regulating clock genes in osteoblasts.Biology open · 2015Article
- Differentiation of Odontoblast-Like Cells From Mouse Induced Pluripotent Stem Cells by Pax9 and Bmp4 Transfection.Stem cells translational medicine · 2015Article
- Obstructive sleep apnea and metabolic bone disease: insights into the relationship between bone and sleep.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2015Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
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Abstract
Several studies have demonstrated that the α1-adrenergic receptor (AR) plays an important role in regulating cell growth and function in osteoblasts. However, the physiological role of α1-AR signaling in bone metabolism is largely unknown. In this study, the stimulation of phenylephrine (PHE), a nonspecific α1-AR agonist, increased the transcriptional factor Nfil3/E4BP4 and led to the rhythmic expression of bone morphogenetic protein 4 (Bmp4) in MC3T3-E1 osteoblastic cells. We also showed that Bmp4 mRNA expression peaked in bone near zeitgeber time 8 in a 24-h rhythm. Furthermore, the expression of Nfil3 and Bmp4 displayed a circadian pattern with opposing phases, which suggested that Nfil3 repressed the expression of the Bmp4 gene during a circadian cycle. On a molecular level, both loss-of-function and gain-of-function experiments demonstrated that Nfil3/E4BP4 negatively regulated Bmp4 expression in osteoblasts. Furthermore, the systemic administration of PHE increased the expression of Nfil3 mRNA in bone, whereas it decreased that of Bmp4 mRNA. The expression of Bmp4 mRNA was decreased significantly by exposure to PHE, and this was concomitant with the increase in Nfil3 binding to the D-box-containing Bmp4 promoter region in MC3T3-E1 cells, which indicates that the expression of Nfil3 by α1-AR signaling can bind directly to the Bmp4 promoter and inhibit Bmp4 expression in osteoblasts. Our results suggest that α1-AR signaling regulates clock genes and Bmp4 expression in osteoblasts. Moreover, α1-AR signaling negatively regulated Bmp4 expression by up-regulating the transcriptional factor Nfil3/E4BP4 in osteoblasts.
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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.