Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction - PubMed (original) (raw)
Targeted ablation of osteocytes induces osteoporosis with defective mechanotransduction
Sawako Tatsumi et al. Cell Metab. 2007 Jun.
Free article
Abstract
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.
Comment in
- Osteocyte messages from a bony tomb.
Bonewald LF. Bonewald LF. Cell Metab. 2007 Jun;5(6):410-1. doi: 10.1016/j.cmet.2007.05.008. Cell Metab. 2007. PMID: 17550775
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