ArticleProceedings of the National Academy of Sciences of the United States of America2008
HCO3-/Cl- anion exchanger SLC4A2 is required for proper osteoclast differentiation and function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 69 citations in OpenAlex.
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- Direct and indirect effects of transforming growth factor-beta on osteoclast-mediated bone remodeling using a new in vitro bone matrix model.JBMR plus · 2025Article
- The structural insight into the functional modulation of human anion exchanger 3.Nature communications · 2024Article
- Potential Theranostic Roles of SLC4 Molecules in Human Diseases.International journal of molecular sciences · 2023Review
- Molecular Mechanisms of Craniofacial and Dental Abnormalities in Osteopetrosis.International journal of molecular sciences · 2023Review
- The structural basis of the pH-homeostasis mediated by the ClNature communications · 2023Article
- Molecular mechanisms, physiological roles, and therapeutic implications of ion fluxes in bone cells: Emphasis on the cation-ClJournal of cellular physiology · 2022Review
- The Evolution of Biomineralization through the Co-Option of Organic Scaffold Forming Networks.Cells · 2022Review
- Systems genetics in diversity outbred mice inform BMD GWAS and identify determinants of bone strength.Nature communications · 2021Article
- Multi-trait GWAS using imputed high-density genotypes from whole-genome sequencing identifies genes associated with body traits in Nile tilapia.BMC genomics · 2021Article
- Membrane Transport Proteins in Osteoclasts: The Ins and Outs.Frontiers in cell and developmental biology · 2021Review
- Positive and negative regulators of osteoclast apoptosis.Bone reports · 2019Review
- KJournal of hematology & oncology · 2019Review
- Cause and effect of microenvironmental acidosis on bone metastases.Cancer metastasis reviews · 2019Review
- Mouse models of SLC4-linked disorders of HCOAmerican journal of physiology. Cell physiology · 2018Review
- Recent advances in osteoclast biology.Histochemistry and cell biology · 2018Review
- CaJournal of immunology (Baltimore, Md. : 1950) · 2018Article
- Targeting Anion Exchange of Osteoclast, a New Strategy for Preventing Wear Particles Induced- Osteolysis.Frontiers in pharmacology · 2018Article
- Review
- Systems Genetic Analyses Highlight a TGFβ-FOXO3 Dependent Striatal Astrocyte Network Conserved across Species and Associated with Stress, Sleep, and Huntington's Disease.PLoS genetics · 2016Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
As the only cell capable of bone resorption, the osteoclast is a central mediator of skeletal homeostasis and disease. To efficiently degrade mineralized tissue, these multinucleated giant cells secrete acid into a resorption lacuna formed between their apical membrane and the bone surface. For each proton pumped into this extracellular compartment, one bicarbonate ion remains in the cytoplasm. To prevent alkalinization of the cytoplasm, a basolateral bicarbonate/chloride exchanger provides egress for intracellular bicarbonate. However, the identity of this exchanger is unknown. Here, we report that the bicarbonate/chloride exchanger, solute carrier family 4, anion exchanger, member 2 (SLC4A2), is up-regulated during osteoclast differentiation. Suppression of Slc4a2 expression by RNA interference inhibits the ability of RAW cells, a mouse macrophage cell line, to differentiate into osteoclasts and resorb mineralized matrix in vitro. Accordingly, Slc4a2-deficient mice fail to remodel the primary, cartilaginous skeletal anlagen. Abnormal multinucleated giant cells are present in the bone marrow of Slc4a2-deficient mice. Though these cells express the osteoclast markers CD68, cathepsin K, and NFATc1, compared with their wild-type (WT) counterparts they are larger, fail to express tartrate-resistant acid phosphatase (TRAP) activity, and display a propensity to undergo apoptosis. In vitro Slc4a2-deficient osteoclasts are unable to resorb mineralized tissue and cannot form an acidified, extracellular resorption compartment. These data highlight SLC4A2 as a critical mediator of osteoclast differentiation and function in vitro and in vivo.
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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.