{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T06:36:53Z","timestamp":1791009413567,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"44","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2008,11,4]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>Slc4a2<\/jats:italic>\n                    expression by RNA interference inhibits the ability of RAW cells, a mouse macrophage cell line, to differentiate into osteoclasts and resorb mineralized matrix\n                    <jats:italic>in vitro<\/jats:italic>\n                    . Accordingly,\n                    <jats:italic>Slc4a2<\/jats:italic>\n                    -deficient mice fail to remodel the primary, cartilaginous skeletal anlagen. Abnormal multinucleated giant cells are present in the bone marrow of\n                    <jats:italic>Slc4a2<\/jats:italic>\n                    -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.\n                    <jats:italic>In vitro Slc4a2<\/jats:italic>\n                    -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\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.0808763105","type":"journal-article","created":{"date-parts":[[2008,10,29]],"date-time":"2008-10-29T21:09:33Z","timestamp":1225314573000},"page":"16934-16939","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":65,"title":["HCO\n                    <sub>3<\/sub>\n                    <sup>\u2212<\/sup>\n                    \/Cl\n                    <sup>\u2212<\/sup>\n                    anion exchanger SLC4A2 is required for proper osteoclast differentiation and function"],"prefix":"10.1073","volume":"105","author":[{"given":"Jing","family":"Wu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases and Immunology, Harvard School of Public Health, 651 Huntington Ave, FXB 205, Boston, MA 02115; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie H.","family":"Glimcher","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, Harvard School of Public Health, 651 Huntington Ave, FXB 205, Boston, MA 02115; and"},{"name":"Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonios O.","family":"Aliprantis","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases and Immunology, Harvard School of Public Health, 651 Huntington Ave, FXB 205, Boston, MA 02115; and"},{"name":"Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2008,11,4]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00157-0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrg1122"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2006.09.023"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S8756-3282(02)00672-5"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra040952"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI113863"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02556011"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2008.03.029"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI35711"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3439"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.13.7835"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1290\/0510075.1"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403779200"},{"key":"e_1_3_3_14_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2474-3-16"},{"key":"e_1_3_3_15_2","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2006.051096"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2005.031765"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2536127100"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI8905"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116032"},{"key":"e_1_3_3_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bone.2007.07.010"},{"key":"e_1_3_3_21_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.4.2126"},{"key":"e_1_3_3_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(01)00206-9"},{"key":"e_1_3_3_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/70563"},{"key":"e_1_3_3_24_2","doi-asserted-by":"publisher","DOI":"10.1242\/dev.122.10.3151"},{"key":"e_1_3_3_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ar.20403"},{"key":"e_1_3_3_26_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.11.072"},{"key":"e_1_3_3_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1096-1132"},{"key":"e_1_3_3_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401466"},{"key":"e_1_3_3_29_2","doi-asserted-by":"publisher","DOI":"10.1136\/mp.50.3.132"},{"key":"e_1_3_3_30_2","doi-asserted-by":"publisher","DOI":"10.1359\/JBMR.051007"},{"key":"e_1_3_3_31_2","first-page":"129","article-title":"Generating murine osteoclasts from bone marrow","volume":"80","author":"Takahashi N","year":"2003","unstructured":"N Takahashi, N Udagawa, S Tanaka, T Suda, Generating murine osteoclasts from bone marrow. Methods Mol Med 80, 129\u2013144 (2003).","journal-title":"Methods Mol Med"},{"key":"e_1_3_3_32_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2001.16.4.788"},{"key":"e_1_3_3_33_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.1997.273.4.F601"},{"key":"e_1_3_3_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.01.040"},{"key":"e_1_3_3_35_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.101.6.2210"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0808763105","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:07:27Z","timestamp":1649786847000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0808763105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,11,4]]},"references-count":35,"journal-issue":{"issue":"44","published-print":{"date-parts":[[2008,11,4]]}},"alternative-id":["10.1073\/pnas.0808763105"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0808763105","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,11,4]]},"assertion":[{"value":"2008-08-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2008-11-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}