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Calcified Tissue International

Erschienen in:

01.12.2008

Characterization of the Bone Phenotype in ClC-7-Deficient Mice

verfasst von: Anita Vibsig Neutzsky-Wulff, Morten A. Karsdal, Kim Henriksen

Erschienen in: Calcified Tissue International | Ausgabe 6/2008

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Abstract

Mice deficient in the chloride channel ClC-7, which is likely involved in acidification of the resorption lacuna, display severe osteopetrosis. To fully characterize the osteopetrotic phenotype, the phenotypes of osteoclasts and osteoblasts were evaluated. ClC-7^−/− mice and their corresponding wild-type littermates were killed at 4–5 weeks of age. Biochemical markers of bone resorption (CTX-I), osteoclast number (TRAP5b), and osteoblast activity (ALP) were evaluated in serum. Splenocytes were differentiated into osteoclasts using M-CSF and RANKL. Mature osteoclasts were seeded on calcified or decalcified bone slices, and CTX-I, Ca²⁺, and TRAP were measured. Acidification rates in membrane vesicles from bone cells were measured using acridine orange. Osteoblastogenesis and nodule formation in vitro were investigated using calvarial osteoblasts. ClC-7^−/− osteoclasts were unable to resorb calcified bone in vitro. However, osteoclasts were able to degrade decalcified bone. Acid influx in bone membrane vesicles was reduced by 70% in ClC-7^−/− mice. Serum ALP was increased by 30% and TRAP5b was increased by 250% in ClC-7^−/− mice, whereas the CTX/TRAP5b ratio was reduced to 50% of the wild-type level. Finally, evaluation of calvarial ClC-7^−/− osteoblasts showed normal osteoblastogenesis. In summary, we present evidence supporting a pivotal role for ClC-7 in acidification of the resorption lacuna and evidence indicating that bone formation and bone resorption are no longer balanced in ClC-7^−/− mice.

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Titel: Characterization of the Bone Phenotype in ClC-7-Deficient Mice
verfasst von: Anita Vibsig Neutzsky-Wulff
Morten A. Karsdal
Kim Henriksen
Publikationsdatum: 01.12.2008
Verlag: Springer-Verlag
Erschienen in: Calcified Tissue International / Ausgabe 6/2008
Print ISSN: 0171-967X
Elektronische ISSN: 1432-0827
DOI: https://doi.org/10.1007/s00223-008-9185-7

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