ArticleeLife2015
Nur77 prevents excessive osteoclastogenesis by inducing ubiquitin ligase Cbl-b to mediate NFATc1 self-limitation.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 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.
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Who cites it
15 citing papers in PubMed, 28 citations in OpenAlex.
- Controversy and multiple roles of the solitary nucleus receptor Nur77 in disease and physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Review
- NOR1 promotes the osteoblastic differentiation of human periodontal ligament stem cells via TGF-β signaling pathway.Cellular and molecular life sciences : CMLS · 2024Article
- Nr4a1 enhances Wnt4 transcription to promote mesenchymal stem cell osteogenesis and alleviates inflammation-inhibited bone regeneration.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Dissection of Cellular Communication between Human Primary Osteoblasts and Bone Marrow Mesenchymal Stem Cells in Osteoarthritis at Single-Cell Resolution.International journal of stem cells · 2023Article
- Strategies of Macrophages to Maintain Bone Homeostasis and Promote Bone Repair: A Narrative Review.Journal of functional biomaterials · 2022Review
- Trim39 regulates neuronal apoptosis by acting as a SUMO-targeted E3 ubiquitin-ligase for the transcription factor NFATc3.Cell death and differentiation · 2022Article
- Nur77 Prevents Osteoporosis by Inhibiting the NF-κB Signalling Pathway and Osteoclast Differentiation.Journal of cellular and molecular medicine · 2022Article
- The Osteogenesis Imperfecta Type V Mutant BRIL/IFITM5 Promotes Transcriptional Activation of MEF2, NFATc, and NR4A in Osteoblasts.International journal of molecular sciences · 2022Article
- NR4A1 counteracts JNK activation incurred by ER stress or ROS in pancreatic β-cells for protection.Journal of cellular and molecular medicine · 2020Article
- Long Noncoding RNA Analyses for Osteoporosis Risk in Caucasian Women.Calcified tissue international · 2019Article
- Updates on Osteoimmunology: What's New on the Cross-Talk Between Bone and Immune System.Frontiers in endocrinology · 2019Review
- mTORC1 impedes osteoclast differentiation via calcineurin and NFATc1.Communications biology · 2018Article
- The multi-faceted role of retinoid X receptor in bone remodeling.Cellular and molecular life sciences : CMLS · 2017Review
- Article
- Gata2 Is a Rheostat for Mesenchymal Stem Cell Fate in Male Mice.Endocrinology · 2016Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Osteoclasts are bone-resorbing cells essential for skeletal remodeling. However, over-active osteoclasts can cause bone-degenerative disorders. Therefore, the level of NFATc1, the master transcription factor of osteoclast, must be tightly controlled. Although the activation and amplification of NFATc1 have been extensively studied, how NFATc1 signaling is eventually resolved is unclear. Here, we uncover a novel and critical role of the orphan nuclear receptor Nur77 in mediating an NFATc1 self-limiting regulatory loop to prevent excessive osteoclastogenesis. Nur77 deletion leads to low bone mass owing to augmented osteoclast differentiation and bone resorption. Mechanistically, NFATc1 induces Nur77 expression at late stage of osteoclast differentiation; in turn, Nur77 transcriptionally up-regulates E3 ubiquitin ligase Cbl-b, which triggers NFATc1 protein degradation. These findings not only identify Nur77 as a key player in osteoprotection and a new therapeutic target for bone diseases, but also elucidate a previously unrecognized NFATc1→Nur77→Cblb-•NFATc1 feedback mechanism that confers NFATc1 signaling autoresolution.
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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.