ArticleThe Journal of clinical investigation2017
RANKL coordinates multiple osteoclastogenic pathways by regulating expression of ubiquitin ligase RNF146.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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
26 citing papers in PubMed, 41 citations in OpenAlex.
- 5-methoxyresorcinol mitigates postmenopausal osteoporosis through regulation of the PI3K-AKT-GSK3β signaling pathway and ROS homeostasis.Frontiers in pharmacology · 2026Article
- Research progress on the intervention of osteoporosis by Chinese herbal monomers based on the Nrf2/NF-κB/MAPK pathway.Frontiers in endocrinology · 2026Review
- Targeting the PARylation-Dependent Ubiquitination Signaling Pathway for Cancer Therapies.Biomolecules · 2025Review
- PARylation-mediated post-transcriptional modifications in cancer immunity and immunotherapy.Frontiers in immunology · 2025Review
- A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and TNKS/2.The Journal of cell biology · 2024Article
- Role of ubiquitination in the occurrence and development of osteoporosis (Review).International journal of molecular medicine · 2024Review
- A genome-wide screen links peroxisome regulation with Wnt signaling through RNF146 and tankyrase.bioRxiv : the preprint server for biology · 2024Article
- Altered Osteogenic Differentiation in Mesenchymal Stem Cells Isolated from Compact Bone of Chicken Treated with Varying Doses of Lipopolysaccharides.Biomolecules · 2023Article
- The role of E3 ubiquitin ligases in bone homeostasis and related diseases.Acta pharmaceutica Sinica. B · 2023Review
- A Review on Pathophysiology, and Molecular Mechanisms of Bacterial Chondronecrosis and Osteomyelitis in Commercial Broilers.Biomolecules · 2023Review
- E3-ubiquitin ligases and recent progress in osteoimmunology.Frontiers in immunology · 2023Review
- The osteoprotective role of USP26 in coordinating bone formation and resorption.Cell death and differentiation · 2022Article
- Tankyrase represses autoinflammation through the attenuation of TLR2 signaling.The Journal of clinical investigation · 2022Article
- E3 Ubiquitin Ligases: Potential Therapeutic Targets for Skeletal Pathology and Degeneration.Stem cells international · 2022Review
- RO4929097 regulates RANKL-induced osteoclast formation and LPS-mediated bone resorption.Aging · 2021Article
- Endonuclease increases efficiency of osteoblast isolation from murine calvariae.Scientific reports · 2021Article
- Inhibition of RANKL-Induced Osteoclastogenesis by Novel Mutant RANKL.International journal of molecular sciences · 2021Article
- RUNX2 Phosphorylation by Tyrosine Kinase ABL Promotes Breast Cancer Invasion.Frontiers in oncology · 2021Article
- LPS-induced inflammation disorders bone modeling and remodeling by inhibiting angiogenesis and disordering osteogenesis in chickens.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Article
- Alveolar Bone Protection by Targeting the SH3BP2-SYK Axis in Osteoclasts.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bone undergoes continuous remodeling due to balanced bone formation and resorption mediated by osteoblasts and osteoclasts, respectively. Osteoclasts arise from the macrophage lineage, and their differentiation is dependent on RANKL, a member of the TNF family of cytokines. Here, we have provided evidence that RANKL controls the expression of 3BP2, an adapter protein that is required for activation of SRC tyrosine kinase and simultaneously coordinates the attenuation of β-catenin, both of which are required to execute the osteoclast developmental program. We found that RANKL represses the transcription of the E3 ubiquitin ligase RNF146 through an NF-κB-related inhibitory element in the RNF146 promoter. RANKL-mediated suppression of RNF146 results in the stabilization of its substrates, 3BP2 and AXIN1, which consequently triggers the activation of SRC and attenuates the expression of β-catenin, respectively. Depletion of RNF146 caused hypersensitivity to LPS-induced TNF-α production in vivo. RNF146 thus acts as an inhibitory switch to control osteoclastogenesis and cytokine production and may be a control point underlying the pathogenesis of chronic inflammatory 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.