ArticleThe Journal of clinical investigation2014
RBP-J imposes a requirement for ITAM-mediated costimulation of osteoclastogenesis.
Article in The Journal of clinical investigation, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 44 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
44 citing papers in PubMed, 57 citations in OpenAlex.
- An RBP-J-heparan sulfate-dependent gatekeeper directs macrophage fate between inflammatory regulation and osteoclastogenesis.bioRxiv : the preprint server for biology · 2026Article
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Metabolic reprogramming in skeletal cell differentiation.Bone research · 2024Review
- The expression of RBPJ and its potential role in rheumatoid arthritis.BMC genomics · 2024Article
- Reciprocal suppression between TGFβ signaling and TNF stimulation finetunes the macrophage inflammatory response.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Jagged1 Acts as an RBP-J Target and Feedback Suppresses TNF-Mediated Inflammatory Osteoclastogenesis.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Article
- Regulation of Osteoclastogenesis and Bone Resorption by miRNAs.Frontiers in cell and developmental biology · 2021Review
- The Potential Role of RP105 in Regulation of Inflammation and Osteoclastogenesis During Inflammatory Diseases.Frontiers in cell and developmental biology · 2021Review
- Def6 regulates endogenous type-I interferon responses in osteoblasts and suppresses osteogenesis.eLife · 2020Article
- Using Genetics in Periodontal Disease to Justify Implant Failure in Down Syndrome Patients.Journal of clinical medicine · 2020Article
- Regulatory network mediated by RBP-J/NFATc1-miR182 controls inflammatory bone resorption.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- Intrinsic Restriction of TNF-Mediated Inflammatory Osteoclastogenesis and Bone Resorption.Frontiers in endocrinology · 2020Review
- Osteoclastogenesis inhibition by mutated IGSF23 results in human osteopetrosis.Cell proliferation · 2019Article
- Identification of a Novel Role for Foxo3 Isoform2 in Osteoclastic Inhibition.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- G-protein GαScientific reports · 2019Article
- The RANKL-RANK Axis: A Bone to Thymus Round Trip.Frontiers in immunology · 2019Review
- Bone protection by inhibition of microRNA-182.Nature communications · 2018Article
- Article
- C/EBPα transcription factor is regulated by the RANK cytoplasmicThe Journal of biological chemistry · 2018Article
Corrections and comments
- Erratum issued
Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Osteoclastogenesis requires activation of RANK signaling as well as costimulatory signals from immunoreceptor tyrosine-based activation motif-containing (ITAM-containing) receptors/adaptors, predominantly tyrosine kinase-binding proteins DAP12 and FcRγ, in osteoclast precursors. It is not well understood how costimulatory signals are regulated and integrated with RANK signaling. Here, we found that osteopetrotic bone phenotypes in mice lacking DAP12 or DAP12 and FcRγ are mediated by the transcription factor RBP-J, as deletion of Rbpj in these mice substantially rescued the defects of bone remodeling. Using a TNF-α-induced model of inflammatory bone resorption, we determined that RBP-J deficiency enables TNF-α to induce osteoclast formation and bone resorption in DAP12-deficient animals. Thus, RBP-J imposes a requirement for ITAM-mediated costimulation of RANKL or TNF-α-induced osteoclastogenesis. Mechanistically, RBP-J suppressed induction of key osteoclastogenic factors NFATc1, BLIMP1, and c-FOS by inhibiting ITAM-mediated expression and function of PLCγ2 and activation of downstream calcium-CaMKK/PYK2 signaling. Moreover, RBP-J suppressed Plcg2 expression and downstream calcium oscillations indirectly by a TGF-β/PLCγ2/calcium axis. Together, our findings indicate that RBP-J suppresses ITAM-mediated costimulation, thereby limiting crosstalk between ITAM and RANK/TNFR signaling and allowing fine tuning of osteoclastogenesis during bone homeostasis and under inflammatory conditions. Furthermore, these data suggest that environmental cues that regulate RBP-J expression/function potentially modulate the requirement for costimulatory signaling for osteoclast differentiation and bone remodeling.
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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.