ArticleBone research2023
IgSF11-mediated phosphorylation of pyruvate kinase M2 regulates osteoclast differentiation and prevents pathological bone loss.
Article in Bone research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Multi-ancestry genome-wide association study of severe pregnancy nausea and vomiting.Nature genetics · 2026Pooled it
- Glucose metabolism in osteoporosis: A potential therapeutic target (Review).International journal of molecular medicine · 2026Review
- Glycolysis in bone remodeling: from energy supply to signaling regulation.Molecular biology reports · 2026Review
- IGSF10 regulates osteogenesis and osteoclastogenesis via a noncanonical EGFR-STAT1 signaling axis to promote skeletal regeneration.Bone research · 2026Article
- Macrophage junctional adhesion molecule-like (JAML) protein promotes NLRP3 inflammasome activation in the development of atherosclerosis.Cell death and differentiation · 2025Article
- [IGSF11: A Novel Target for Cancer Immunotherapy].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Review
- PKM2 regulates osteoclastogenesis by affecting osteoclast precursor cell fusion via downregulation of OC-STAMP and DC-STAMP.The Journal of biological chemistry · 2025Article
- VSIG-3/IGSF11 silencing in A2058 melanoma cells simultaneously suppresses melanoma progression and induces anti-tumoral cytokine profile in human T cells: In silico and in vitro study.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Selective Modulation of Osteoclast Function byToxins · 2025Article
- The impact of IgSF11-PKM2 pathway on gene expression in osteoclasts.microPublication biology · 2025Article
- Immunomodulatory Mechanisms of Rehmanniae Radix Praeparata-Achyranthes Root-Chinese Angelica Root Combination in Nontraumatic Osteonecrosis of the Femoral Head: A Comprehensive Network Pharmacology and Molecular Docking Study Focusing on Immunological Pathways.Mediators of inflammation · 2025Article
- Multi-ancestry GWAS of severe pregnancy nausea and vomiting identifies risk loci associated with appetite, insulin signaling, and brain plasticity.Research square · 2024Article
- Multi-ancestry GWAS of severe pregnancy nausea and vomiting identifies risk loci associated with appetite, insulin signaling, and brain plasticity.medRxiv : the preprint server for health sciences · 2024Article
- Unraveling the intricacies of osteoclast differentiation and maturation: insight into novel therapeutic strategies for bone-destructive diseases.Experimental & molecular medicine · 2024Review
- Extraordinary diversity of the CD28/CTLA4 family across jawed vertebrates.Frontiers in immunology · 2024Article
- Targeting pyruvate kinase M2 for the treatment of kidney disease.Frontiers in pharmacology · 2024Review
- IgSF11 deficiency alleviates osteoarthritis in mice by suppressing early subchondral bone changes.Experimental & molecular medicine · 2023Article
- Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Osteoclasts are primary bone-resorbing cells, and receptor-activated NF-kB ligand (RANKL) stimulation is the key driver of osteoclast differentiation. During late-stage differentiation, osteoclasts become multinucleated and enlarged (so-called "maturation"), suggesting their need to adapt to changing metabolic demands and a substantial increase in size. Here, we demonstrate that immunoglobulin superfamily 11 (IgSF11), which is required for osteoclast differentiation through an association with the postsynaptic scaffolding protein PSD-95, regulates osteoclast differentiation by controlling the activity of pyruvate kinase M isoform 2 (PKM2). By using a system that directly induces the activation of IgSF11 in a controlled manner, we identified PKM2 as a major IgSF11-induced tyrosine-phosphorylated protein. IgSF11 activates multiple Src family tyrosine kinases (SFKs), including c-Src, Fyn, and HcK, which phosphorylate PKM2 and thereby inhibit PKM2 activity. Consistently, IgSF11-deficient cells show higher PKM2 activity and defective osteoclast differentiation. Furthermore, inhibiting PKM2 activities with the specific inhibitor Shikonin rescues the impaired osteoclast differentiation in IgSF11-deficient cells, and activating PKM2 with the specific activator TEPP46 suppresses osteoclast differentiation in wild-type cells. Moreover, PKM2 activation further suppresses osteoclastic bone loss without affecting bone formation in vivo. Taken together, these results show that IgSF11 controls osteoclast differentiation through PKM2 activity, which is a metabolic switch necessary for optimal osteoclast maturation.
Identifiers
What Socratic 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 Socratic graph.