Characterization of the bone phenotype in ClC-7-deficient mice.

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, Ca(2+), 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.

journal_name

Calcif Tissue Int

authors

Neutzsky-Wulff AV,Karsdal MA,Henriksen K

doi

10.1007/s00223-008-9185-7

subject

Has Abstract

pub_date

2008-12-01 00:00:00

pages

425-37

issue

6

eissn

0171-967X

issn

1432-0827

journal_volume

83

pub_type

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