{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T20:46:36Z","timestamp":1774644396958,"version":"3.50.1"},"reference-count":34,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2006,7,1]],"date-time":"2006-07-01T00:00:00Z","timestamp":1151712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To assess the role of Cl\u2212 transport during osteoclastic bone resorption, we studied the expression and function of K+\/Cl\u2212 co-transporters (KCCs). KCC1 and chloride channel-7 were found to be expressed in mouse osteoclasts. The KCC inhibitor, R(+)-butylindazone (DIOA), KCC1 antisense oligo-nucleotides, and siRNA suppressed osteoclastic pit formation. DIOA also decreased Cl\u2212 extrusion and reduced H+ extrusion activity. These results show that KCC1 provides a Cl\u2212 extrusion mechanism accompanying the H+ extrusion during bone resorption.<\/jats:p>\n               <jats:p>Introduction: Mice with deficient chloride (Cl\u2212) channels, ClC7, show severe osteopetrosis, resulting from impairment of Cl\u2212 extrusion during osteoclastic bone resorption. However, the expression and functional role of Cl\u2212 transporters other than ClC7 in mammalian osteoclasts is unknown. The aim of this study was to determine expression of K+\/Cl\u2212 co-transporters (KCCs) and their functional role for bone resorption in mouse osteoclasts.<\/jats:p>\n               <jats:p>Materials and Methods: Mouse osteoclasts were derived from cultured bone marrow cells with macrophage-colony stimulating factor (M-CSF) and RANKL or from co-culture of bone marrow cells and primary osteoblasts. We examined the expression of Cl\u2212 transporters using RT-PCR, immunochemical, and Western blot methods. The effects of Cl\u2212 transport inhibitors on H+ and Cl\u2212 extrusion were assessed by measuring intracellular H+ ([H+]i) and Cl\u2212 ([Cl\u2212]i). The effects of inhibitors, antisense oligo-nucleotides, and siRNA for Cl\u2212 transporters on bone resorption activities were evaluated using a pit formation assay.<\/jats:p>\n               <jats:p>Results and Conclusions: Mouse osteoclasts express not only ClC7 but also K+\/Cl\u2212 co-transporter mRNA. The existence of KCC1 in the cell membrane of mouse osteoclasts was confirmed by immunochemical staining and Western blot analysis. KCC inhibitors and Cl\u2212 channels blockers increased [Cl\u2212]i and [H+]i in resorbing osteoclasts, suggesting that the suppression of Cl\u2212 extrusion through KCC and Cl\u2212 channels leads to reduced H+ extrusion activity. The combination of both inhibitors greatly suppressed these extrusion activities. KCC inhibitors and Cl\u2212 channel blockers also decreased osteoclastic bone resorption in our pit area essay. Furthermore, KCC1 antisense oligo-nucleotides and siRNA suppressed osteoclastic pit formation as well as treatment of ClC7 inhibitors. These results indicate that K+\/Cl\u2212 co-transporter-1 expressed in mouse osteoclasts acts as a Cl\u2212 extruder and plays an important role for H+ extrusion during bone resorption.<\/jats:p>","DOI":"10.1359\/jbmr.060407","type":"journal-article","created":{"date-parts":[[2006,7,4]],"date-time":"2006-07-04T05:47:20Z","timestamp":1151992040000},"page":"984-992","source":"Crossref","is-referenced-by-count":19,"title":["Expression of Mouse Osteoclast K-Cl Co-Transporter-1 and Its Role During Bone Resorption"],"prefix":"10.1093","volume":"21","author":[{"given":"Hiroshi","family":"Kajiya","sequence":"first","affiliation":[{"name":"Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fujio","family":"Okamoto","sequence":"additional","affiliation":[{"name":"Department of Physiological Science and Molecular Biology, Fukuoka Dental College, Fukuoka, 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