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Publication : Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction.

First Author  Tatsumi S Year  2007
Journal  Cell Metab Volume  5
Issue  6 Pages  464-75
PubMed ID  17550781 Mgi Jnum  J:129907
Mgi Id  MGI:3770371 Doi  10.1016/j.cmet.2007.05.001
Citation  Tatsumi S, et al. (2007) Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction. Cell Metab 5(6):464-75
abstractText  Bone remodeling is performed by osteoclasts and osteoblasts at the bone surface. Inside of bone is a network of numerous osteocytes, whose specific function has remained an enigma. Here we describe a transgenic mouse model in which inducible and specific ablation of osteocytes is achieved in vivo through targeted expression of diphtheria toxin (DT) receptor. Following a single injection of DT, approximately 70%-80% of the osteocytes, but apparently no osteoblasts, were killed. Osteocyte-ablated mice exhibited fragile bone with intracortical porosity and microfractures, osteoblastic dysfunction, and trabecular bone loss with microstructural deterioration and adipose tissue proliferation in the marrow space, all of which are hallmarks of the aging skeleton. Strikingly, these 'osteocyte-less' mice were resistant to unloading-induced bone loss, providing evidence for the role of osteocytes in mechanotransduction. Thus, osteocytes represent an attractive target for the development of diagnostics and therapeutics for bone diseases, such as osteoporosis.
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