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During proton pumping, intracellular pH (pH\n                    <jats:sub>i<\/jats:sub>\n                    ) is thought to be kept at a near\u2010neutral level by chloride\/bicarbonate exchange. Here we show that the Na\n                    <jats:sup>+<\/jats:sup>\n                    \u2010independent chloride\/bicarbonate anion exchanger 2 (Ae2) is relevant for this process in the osteoclasts from the longbonesof\n                    <jats:italic>\n                      Ae2\n                      <jats:sub>a,b<\/jats:sub>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice (deficient in the main isoforms Ae2a, Ae2b\n                    <jats:sub>1<\/jats:sub>\n                    , and Ae2b\n                    <jats:sub>2<\/jats:sub>\n                    ). Although the long bones of these mice had normal numbers of multinucleated osteoclasts, these cells lacked a ruffled border and displayed impaired bone resorption activity, resulting in an osteopetrotic phenotype of long bones. Moreover,\n                    <jats:italic>in vitro<\/jats:italic>\n                    osteoclastogenesis assays using long\u2010bone marrow cells from\n                    <jats:italic>\n                      Ae2\n                      <jats:sub>a,b<\/jats:sub>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice suggested a role for Ae2 in osteoclast formation, as fusion of preosteoclasts for the generation of active multinucleated osteoclasts was found to be slightly delayed. In contrast to the abnormalities observed in the long bones, the skull of\n                    <jats:italic>\n                      Ae2\n                      <jats:sub>a,b<\/jats:sub>\n                      <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    <\/jats:italic>\n                    mice showed no alterations, indicating that calvaria osteoclasts may display normal resorptive activity. Microfluorimetric analysis of osteoclasts from normal mice showed that, in addition to Ae2 activity, calvaria osteoclasts\u2014but not long\u2010bone osteoclasts\u2014possess a sodium\u2010dependent bicarbonate transporting activity. Possibly, this might compensate for the absence of Ae2 in calvaria osteoclasts of\n                    <jats:italic>\n                      Ae2\n                      <jats:sub>a,<\/jats:sub>\n                    <\/jats:italic>\n                    <jats:sub>b<\/jats:sub>\n                    <jats:sup>\u2013\/\u2013<\/jats:sup>\n                    mice.\u2014Jansen, I. D. C., Mardones, P., Lecanda, F., de Vries, T. J., Recalde, S., Hoeben, K. A., Schoenmaker, T., Ravesloot, J.\u2010H., van Borren, M. M. G. J., van Eijden, T. M., Bronckers, A. L. J. J., Kellokumpu, S., Medina, J. F., Everts, V., Oude Elferink, R. P. J. Ae2\n                    <jats:sub>a,b<\/jats:sub>\n                    \u2010Deficient mice exhibit osteopetrosis of long bones but not of calvaria.\n                    <jats:italic>FASEB J<\/jats:italic>\n                    . 23, 3470\u20133481 (2009).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.08-122598","type":"journal-article","created":{"date-parts":[[2009,6,29]],"date-time":"2009-06-29T20:46:34Z","timestamp":1246308394000},"page":"3470-3481","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":60,"title":["Ae2\n                    <sub>a,b<\/sub>\n                    \u2010Deficient mice exhibit osteopetrosis of long bones but not of calvaria"],"prefix":"10.1096","volume":"23","author":[{"given":"Ineke D. C.","family":"Jansen","sequence":"first","affiliation":[{"name":"Department of Periodontology Academic Centre for Dentistry Amsterdam University of Amsterdam and VU University Amsterdam Research Institute MOVE Amsterdam The Netherlands"},{"name":"Department of Oral Cell Biology Academic Centre for Dentistry Amsterdam University of Amsterdam and VU University Amsterdam Research Institute MOVE Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Mardones","sequence":"additional","affiliation":[{"name":"AMC Liver Center Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Lecanda","sequence":"additional","affiliation":[{"name":"School of Medicine and Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA) University of Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teun J.","family":"de Vries","sequence":"additional","affiliation":[{"name":"Department of Periodontology Academic Centre for Dentistry Amsterdam University of Amsterdam and VU University Amsterdam Research Institute MOVE Amsterdam The Netherlands"},{"name":"Department of Oral Cell Biology Academic Centre for Dentistry Amsterdam University of Amsterdam and VU University Amsterdam Research Institute MOVE Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Recalde","sequence":"additional","affiliation":[{"name":"School of Medicine and Centro de Investigaci\u00f3n M\u00e9dica Aplicada (CIMA) University of Navarra Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees A.","family":"Hoeben","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Histology Academic Medical Center University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ton","family":"Schoenmaker","sequence":"additional","affiliation":[{"name":"Department of Periodontology Academic Centre for Dentistry Amsterdam University of Amsterdam and VU University Amsterdam Research Institute MOVE Amsterdam The Netherlands"},{"name":"Department of Oral Cell Biology Academic Centre for Dentistry Amsterdam University of Amsterdam and VU University Amsterdam Research Institute MOVE Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan-Hindrik","family":"Ravesloot","sequence":"additional","affiliation":[{"name":"Department of Physiology Academic Medical Center University of Amsterdam Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcel M. 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