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- Title
Ae2<sub>a,b</sub>-Deficient mice exhibit osteopetrosis of long bones but not of calvaria.
- Authors
Jansen, Ineke D. C.; Mardones, Pablo; Lecanda, Fernando; De Vries, Teun J.; Recalde, Sergio; Hoeben, Kees A.; Schoenmaker, Ton; Ravesloot, Jan-Hindrik; Van Borren, Marcel M. G. J.; Van Eijden, Theo M.; Bronckers, Antonius L. J. J.; Kellokumpu, Sakari; Medina, Juan F.; Everts, Vincent; Elferink, Ronald P. J. Oude
- Abstract
Extracellular acidification by osteoclasts is essential to bone resorption. During proton pumping, intracellular pH (pHi) is thought to be kept at a near-neutral level by chloride/bicarbonate exchange. Here we show that the Na+-independent chloride/bicarbonate anion exchanger 2 (Ae2) is relevant for this process in the osteoclasts from the long bones of Ae2a,b-/- mice (deficient in the main isoforms Ae2a, Ae2b1, and Ae2b2). 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 pheno-type of long bones. Moreover, in vitro osteoclastogenesis assays using long-bone marrow cells from Ae2a,b-/- 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 Ae2a,b-/- 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---but not long-bone osteoclasts--possess a sodium-dependent bicarbonate transporting activity. Possibly, this might compensate for the absence of Ae2 in calvaria osteoclasts of Ae2a,b-/- mice.
- Subjects
OSTEOPETROSIS; LABORATORY mice; ION exchange (Chemistry); OSTEOCLASTS; CALVARIA; ACIDIFICATION; BONE resorption; BONE marrow cells
- Publication
FASEB Journal, 2009, Vol 23, Issue 10, p3470
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.08-122598