ArticleThe Journal of clinical investigation2014
Chloroquine reduces osteoclastogenesis in murine osteoporosis by preventing TRAF3 degradation.
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. Cited by 81 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
81 citing papers in PubMed, 2 syntheses or guidelines pooled it, 161 citations in OpenAlex.
- From mechanisms to therapeutics: a narrative review on pyroptosis and autophagy in osteoporosis.Annals of medicine · 2025Pooled it
- A multiethnic whole genome sequencing study to identify novel loci for bone mineral density.Human molecular genetics · 2022Pooled it
- A RANKLBone research · 2026Article
- Cell signaling and transcriptional regulation of osteoclast lineage commitment, differentiation, bone resorption and diseases.Cell discovery · 2026Review
- Effects of silybin on triptorelin-induced bone metabolic abnormalities in prostate cancer revealed based on TMT-based proteomics.PloS one · 2026Article
- Otubain 2 stabilizes TNF‑receptor associated factor 3 to accelerate bone fracture healing.Molecular medicine reports · 2025Article
- Effects of chloroquine and hydroxychloroquine on bone health (Review).Molecular medicine reports · 2025Review
- Programmed Cell Death in Rheumatoid Arthritis.Journal of inflammation research · 2025Review
- TNF receptor-associated factors: promising targets of natural products for the treatment of osteoporosis.Frontiers in physiology · 2025Review
- Single cell RNA-sequencing identified CCR7+/RELB+/IRF1+ T cell responding for juvenile idiopathic arthritis pathogenesis.Frontiers in immunology · 2025Article
- TGF-β3 Restrains Osteoclastic Resorption Through Autophagy.Bioengineering (Basel, Switzerland) · 2024Article
- Article
- Hydroxychloroquine and a low activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects.Research square · 2024Article
- Design of Nanodrug Delivery Systems for Tumor Bone Metastasis.Current pharmaceutical design · 2024Review
- The effects of hydroxychloroquine-induced oxidative stress on fracture healing in an experimental rat model.Joint diseases and related surgery · 2024Article
- Coenzyme Q10 prevents RANKL-induced osteoclastogenesis by promoting autophagy via inactivation of the PI3K/AKT/mTOR and MAPK pathways.Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologica · 2024Article
- Nuclear Factor-Kappa B Regulation of Osteoclastogenesis and Osteoblastogenesis.Endocrinology and metabolism (Seoul, Korea) · 2023Article
- Bioactive silica nanoparticles target autophagy, NF-κB, and MAPK pathways to inhibit osteoclastogenesis.Biomaterials · 2023Article
- Rubiadin-1-methyl ether inhibits BECN1 transcription and Beclin1-dependent autophagy during osteoclastogenesis by inhibiting NF-κB p65 activation.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Hydroxychloroquine induces oxidative stress and impairs fracture healing in rats.Joint diseases and related surgery · 2023Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The cytokines RANKL and TNF activate NF-κB signaling in osteoclast precursors (OCPs) to induce osteoclast (OC) formation. Conversely, TNF can limit OC formation through NF-κB p100, which acts as an inhibitor, and TNF receptor-associated receptor 3 (TRAF3); however, a role for TRAF3 in RANKL-mediated OC formation is unknown. We found that TRAF3 limits RANKL-induced osteoclastogenesis by suppressing canonical and noncanonical NF-κB signaling. Conditional OC-specific Traf3-KO (cKO) mice had mild osteoporosis and increased OC formation. RANKL induced TRAF3 degradation via the lysosome/autophagy system. The autophagy/lysosome inhibitor chloroquine reduced RANKL-induced OC formation and function by increasing TRAF3 expression in OCPs in vitro and in vivo. Although chloroquine had no effect on basal bone resorption, it inhibited parathyroid hormone- and ovariectomy-induced OC activation in WT, but not cKO, mice. Deletion of the transcription factor gene Relb resulted in increased TRAF3 expression in OCPs, which was associated with decreased RANKL-induced TRAF3 degradation. RelB directly increased expression of BECN1, a key autophagy regulator, by binding to its promoter. These data indicate that autophagic/lysosomal degradation of TRAF3 is an important step in RANKL-induced NF-κB activation in OCPs. Furthermore, treatments that increase TRAF3 levels in OCPs, including pharmacological inhibition of its degradation with compounds such as chloroquine, may limit bone destruction in common bone diseases.
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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.