Downregulation of Small GTPase Rab7 Impairs Osteoclast Polarization and Bone Resorption

During skeletal growth and remodeling the mineralized bone matrix is resorbed by osteoclasts through the constant secretion of protons and proteases to the bone surface. This relies on the formation of specialized plasma membrane domains, the sealing zone and the ruffled border, and vectorial transp...

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Bibliographic Details
Published in:The Journal of biological chemistry 2001-10, Vol.276 (42), p.39295-39302
Main Authors: Zhao, H, Laitala-Leinonen, T, Parikka, V, Väänänen, H K
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Animals, Newborn
Blotting, Western
Bone Resorption
Cattle
Cells, Cultured
Dose-Response Relationship, Drug
Down-Regulation
Extracellular Matrix - metabolism
Microscopy, Confocal
Microscopy, Electron
Microscopy, Fluorescence
Molecular Sequence Data
Oligonucleotides - metabolism
Oligonucleotides, Antisense - metabolism
Osteoclasts - metabolism
Protein Binding
rab GTP-Binding Proteins - metabolism
Rab7 protein
Rats
RNA, Messenger - metabolism
Time Factors
Transferrin - metabolism
Transferrin - pharmacokinetics
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Summary:During skeletal growth and remodeling the mineralized bone matrix is resorbed by osteoclasts through the constant secretion of protons and proteases to the bone surface. This relies on the formation of specialized plasma membrane domains, the sealing zone and the ruffled border, and vectorial transportation of intracellular vesicles in bone-resorbing osteoclasts. Here we show that Rab7, a small GTPase that is associated with late endosomes, is highly expressed and is predominantly localized at the ruffled border in bone-resorbing osteoclasts. The decreased expression of Rab7 in cultured osteoclasts by antisense oligodeoxynucleotides disrupted the polarization of the osteoclasts and the targeting of vesicles to the ruffled border. These impairments caused a significant inhibition of bone resorption in vitro . The results indicate that the late endocytotic pathway is involved in the osteoclast polarization and bone resorption and underscore the importance of Rab7 in osteoclast function.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M010999200