Article

Mice lacking the integrin beta5 subunit have accelerated osteoclast maturation and increased activity in the estrogen-deficient state.

Department of Medicine, University of California at San Francisco, San Francisco, California 94143, USA.
Journal of Bone and Mineral Research (impact factor: 6.37). 02/2005; 20(1):58-66. DOI:10.1359/JBMR.041017 pp.58-66
Source: PubMed

ABSTRACT Integrin alphavbeta5 is expressed on osteoclast precursors and is capable of recognizing the same amino acid motif as alphavbeta3. Three-month-old beta5(-/-) female OVX mice had increased osteoclastogenesis ex vivo, and microCT assessment of trabecular bone volume was 53% lower than WT-OVX animals. These preliminary data suggest alphavbeta5 integrin's presence on osteoclast precursors may inhibit of osteoclast formation.
Osteoclasts are unique resorptive skeletal cells, capable of degrading bone on contact to the juxtaposed matrix. Integrin alphavbeta5 is expressed on osteoclast precursors, structurally similar to alphavbeta3, and capable of recognizing the same amino acid motif. Given the structural relationship and reciprocal regulation of alphavbeta3 and alphavbeta5, the purpose of this study was to evaluate how alphavbeta5 might contribute to osteoclast maturation and activity.
Three-month-old wildtype (WT) and beta5(-/-) female mice had ovariectomy (OVX) or sham operations. The osteoclastogenic capacity of marrow-derived precursors, the kinetic, the circulating, and structural parameters of bone remodeling, was determined after 6 weeks of paired feeding.
OVX increased osteoclastogenesis ex vivo and in vivo. Osteoclast formation and prolonged pre-osteoclast survival were substantially enhanced in cultures containing beta5(-/-) cells whether obtained from sham-operated or OVX mice. Expression of cathepsin K, beta3 integrin subunit, and calcitonin receptor were accelerated in cultured beta5(-/-)osteoclasts. beta5(-/-) osteoclasts from OVX animals showed a 3-fold enhancement of net resorptive activity, with quantitative muCT showing trabecular bone volume loss after OVX 53% greater in beta5(-/-) OVX compared with similarly treated WT OVX mice (p < 0.05). alpha5beta3 seems to be an inhibitor of osteoclast formation, in contrast to alphavbeta3. In addition, loss of alphavbeta5 seems to accelerate osteoclast formation in the OVX model. Further examination of alphavbeta5 signaling pathways may enhance our understanding of the activation of bone resorption.

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Keywords

alphavbeta5 integrin's presence
 
alphavbeta5 signaling pathways
 
amino acid motif
 
beta3 integrin subunit
 
bone resorption
 
cultured beta5(-/-)osteoclasts
 
Integrin alphavbeta5
 
juxtaposed matrix
 
marrow-derived precursors
 
net resorptive activity
 
osteoclast precursors
 
osteoclastogenesis ex vivo
 
osteoclastogenic capacity
 
OVX 53% greater
 
OVX model
 
quantitative muCT
 
sham operations
 
Three-month-old beta5(-/-)
 
trabecular bone volume
 
WT OVX mice