Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-2-21
pubmed:abstractText
Glucocorticoids (GCs) inhibit the resorptive capacity of the osteoclast by disrupting its cytoskeleton. We find that calpain-6 (Capn6), a unique, nonproteolytic member of its family, is suppressed 12-fold by dexamethasone (DEX) in the bone-degrading cell. While Capn6 abundance parallels commitment of naive bone marrow macrophages (BMMs) to the osteoclast phenotype, its excess or deletion does not affect the cell's differentiation. On the other hand, Capn6 localizes to the sealing zone, and its overexpression promotes osteoclast spreading and large actin ring formation, eventuating in stimulated bone degradation. Conversely, Capn6 knockdown impairs cytoskeletal organization and the cell's resorptive capacity. Capn6 complexes with tubulin, and its absence inhibits microtubule acetylation and stability in the osteoclast. Knockdown of Capn6 also reduces ?(3)-integrin subunit protein, another essential regulator of osteoclast cytoskeletal function. Reflecting Capn6 as a target molecule of GCs, microtubule stability and acetylation, as well as the expression of ?(3)-integrin protein, are similarly suppressed in DEX-treated osteoclasts. Moreover, overexpression of Capn6 rescues GC-mediated disruption of osteoclast cytoskeleton. Thus Capn6 promotes cytoskeletal organization and microtubule stability in osteoclasts, and its inhibition may mediate the resorption-arresting properties of GCs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1523-4681
pubmed:author
pubmed:copyrightInfo
Copyright © 2011 American Society for Bone and Mineral Research.
pubmed:issnType
Electronic
pubmed:volume
26
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
657-65
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Calpain-6, a target molecule of glucocorticoids, regulates osteoclastic bone resorption via cytoskeletal organization and microtubule acetylation.
pubmed:affiliation
Skeletal Diseases Genome Research Center, Kyungpook National University Hospital, Daegu, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural