ArticleThe Journal of clinical investigation2020
Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers.
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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
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Who cites it
122 citing papers in PubMed, 179 citations in OpenAlex.
- C-type lectin receptors: bone remodeling and therapeutic potential.Bone research · 2026Review
- DAMPs, PAMPs, and Alarmins: From Mechanism to Therapy.MedComm · 2026Review
- Cell Type-Specific Ferroptosis Regulatory Networks in the Bone Microenvironment: Implications for the Pathogenesis and Treatment of Osteoporosis.Traffic (Copenhagen, Denmark) · 2026Review
- Mechanism-Oriented Biomaterial Strategies for Bone Regeneration in BRONJ: From Pathological Barriers to Evidence-Matched Repair.Biomolecules · 2026Review
- Apoptosis of Mdm2-deficient osteocytes enhances osteogenesis through TRPM8-enriched apoptotic vesicles.Bone research · 2026Article
- LncH19 regulates osteoclast activation by targeting miR-196a-5p to diagnose postmenopausal osteoporosis.Irish journal of medical science · 2026Article
- Roxadustat Inhibits Osteoclast Differentiation and Function by Disrupting Cell Cycle Exit.International journal of molecular sciences · 2026Article
- Th17/IL-17A Drives Alveolar Bone Loss via the JAK/STAT3-RANKL Axis in the Periodontal Ligament.Oral diseases · 2026Article
- An immunomodulatory bioactive glass orchestrates early bone healing via coordinated macrophage polarization and osteogenesis-osteolysis balance.Materials today. Bio · 2026Article
- Upper lumbar standardized subcutaneous fat index: a novel sex-independent indicator of bone mineral density and musculoskeletal fat infiltration.BMC musculoskeletal disorders · 2026Article
- CFTR mediates ClNature communications · 2026Article
- Osteocyte Cell-Cell Communication Within and Beyond Bone.Current osteoporosis reports · 2026Review
- Osteoblast-derived osteomodulin restrains osteoclastogenesis via ITGB8/RRM2-mediated reduction of mitochondrial respiration and mitochondrial ATP production.Experimental & molecular medicine · 2026Article
- Article
- Osteoimmune microenvironmental failure in osteonecrosis of the femoral head: a necrosis-inflammation-repair loop and immune-editing-inspired framework for hip preservation.Frontiers in immunology · 2026Review
- Translational Nanomedicine for Osteoporosis: Bridging Bone Signaling Networks and Targeted Delivery Systems.International journal of nanomedicine · 2026Review
- Greening Bone Healing: The Emerging Role of Plant-Derived Exosome-Like Nanoparticles in Osteoporosis and Osteoarthritis Therapy.International journal of nanomedicine · 2026Review
- Social isolation, loneliness, genetic susceptibility, and the hazard of incident osteoporosis.International journal of surgery (London, England) · 2026Article
- Fabrication of Lithium/Strontium-Releasing Smart Bioactive Glasses with Anti-Inflammatory and Osteogenic Effects Tailored to Pathological Stages.Macromolecular bioscience · 2025Article
- Exploring the pathogenesis of steroid-induced osteonecrosis of the femoral head co-regulated by mesenchymal stem cells and pyroptosis-related genes with the use of transcriptome.European journal of medical research · 2025Article
62 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the control of bone-resorbing osteoclasts through osteocyte-derived RANKL is well defined, little is known about the regulation of osteoclasts by osteocyte death. Indeed, several skeletal diseases, such as bone fracture, osteonecrosis, and inflammation are characterized by excessive osteocyte death. Herein we show that osteoclasts sense damage-associated molecular patterns (DAMPs) released by necrotic osteocytes via macrophage-inducible C-type lectin (Mincle), which induced their differentiation and triggered bone loss. Osteoclasts showed robust Mincle expression upon exposure to necrotic osteocytes in vitro and in vivo. RNA sequencing and metabolic analyses demonstrated that Mincle activation triggers osteoclastogenesis via ITAM-based calcium signaling pathways, skewing osteoclast metabolism toward oxidative phosphorylation. Deletion of Mincle in vivo effectively blocked the activation of osteoclasts after induction of osteocyte death, improved fracture repair, and attenuated inflammation-mediated bone loss. Furthermore, in patients with osteonecrosis, Mincle was highly expressed at skeletal sites of osteocyte death and correlated with strong osteoclastic activity. Taken together, these data point to what we believe is a novel DAMP-mediated process that allows osteoclast activation and bone loss in the context of osteocyte death.
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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.