ArticleProceedings of the National Academy of Sciences of the United States of America2009
Targeted disruption of the Cl-/HCO3- exchanger Ae2 results in osteopetrosis in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 45 citations in OpenAlex.
- Spectrum and functions of ion channels and transporters in osteoclasts.Bone research · 2026Review
- The developmental remodeling front: resorptive cell-vascular coupling at the chondro-osseous junction.Frontiers in cell and developmental biology · 2026Review
- Energy-Dependent Phosphate and Acid Transport for Bone Formation and Resorption.Journal of cellular biochemistry · 2025Review
- The role of NaPflugers Archiv : European journal of physiology · 2024Review
- Molecular mechanisms, physiological roles, and therapeutic implications of ion fluxes in bone cells: Emphasis on the cation-ClJournal of cellular physiology · 2022Review
- Aesculetin Inhibits Osteoclastic Bone Resorption through Blocking Ruffled Border Formation and Lysosomal Trafficking.International journal of molecular sciences · 2020Article
- Mouse models of SLC4-linked disorders of HCOAmerican journal of physiology. Cell physiology · 2018Review
- Genetic disorders in beef cattle: a review.Genes & genomics · 2017Review
- Article
- Bovine parathyroid hormone enhances osteoclast bone resorption by modulating V-ATPase through PTH1R.International journal of molecular medicine · 2016Article
- A single simple procedure for dewaxing, hydration and heat-induced epitope retrieval (HIER) for immunohistochemistry in formalin fixed paraffin-embedded tissue.European journal of histochemistry : EJH · 2015Article
- Taxonomy of rare genetic metabolic bone disorders.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2015Article
- Dental and Cranial Pathologies in Mice Lacking the Cl(-) /H(+) -Exchanger ClC-7.Anatomical record (Hoboken, N.J. : 2007) · 2015Article
- Osteopetrorickets due to Snx10 deficiency in mice results from both failed osteoclast activity and loss of gastric acid-dependent calcium absorption.PLoS genetics · 2015Article
- Painful boney metastases.The Korean journal of pain · 2013Article
- The divergence, actions, roles, and relatives of sodium-coupled bicarbonate transporters.Physiological reviews · 2013Review
- SLC4A2-mediated Cl-/HCO3- exchange activity is essential for calpain-dependent regulation of the actin cytoskeleton in osteoclasts.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- High bone mass in the STR/ort mouse results from increased bone formation and impaired bone resorption and is associated with extramedullary hematopoiesis.Journal of bone and mineral metabolism · 2013Article
- Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption--implications for osteoclast quality.BMC musculoskeletal disorders · 2010Article
- A deletion mutation in bovine SLC4A2 is associated with osteopetrosis in Red Angus cattle.BMC genomics · 2010Article
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Authors and funding
8 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Osteoclasts are multinucleated bone-resorbing cells responsible for constant remodeling of bone tissue and for maintaining calcium homeostasis. The osteoclast creates an enclosed space, a lacuna, between their ruffled border membrane and the mineralized bone. They extrude H(+) and Cl(-) into these lacunae by the combined action of vesicular H(+)-ATPases and ClC-7 exchangers to dissolve the hydroxyapatite of bone matrix. Along with intracellular production of H(+) and HCO(3)(-) by carbonic anhydrase II, the H(+)-ATPases and ClC-7 exchangers seems prerequisite for bone resorption, because genetic disruption of either of these proteins leads to osteopetrosis. We aimed to complete the molecular model for lacunar acidification, hypothesizing that a HCO(3)(-) extruding and Cl(-) loading anion exchange protein (Ae) would be necessary to sustain bone resorption. The Ae proteins can provide both intracellular pH neutrality and serve as cellular entry mechanism for Cl(-) during bone resorption. Immunohistochemistry revealed that Ae2 is exclusively expressed at the contra-lacunar plasma membrane domain of mouse osteoclast. Severe osteopetrosis was encountered in Ae2 knockout (Ae2-/-) mice where the skeletal development was impaired with a higher diffuse radio-density on x-ray examination and the bone marrow cavity was occupied by irregular bone speculae. Furthermore, osteoclasts in Ae2-/- mice were dramatically enlarged and fail to form the normal ruffled border facing the lacunae. Thus, Ae2 is likely to be an essential component of the bone resorption mechanism in osteoclasts.
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