Role of Klotho in Osteoporosis and Renal Osteodystrophy
Abstract
The most significant findings to date are from mice with Klotho ablated specifically from long bones. First, we found that loss of Klotho in bone disrupts normal bone development. Histological analyses showed that bones of 6-week old Prx1cre;Klothofl/fl mice have normal cortical bone but scarce trabeculae relative to controls. In particular, male Prx1cre;Klothofl/fl mice had reduced bone volume/total volume. The loss was more pronounced at 6 than 24 weeks. This effect was confirmed by in vitro analysis with isolated primary osteoblasts treated to delete Klotho that exhibited a defect in bone mineralization. Moreover, male Prx1cre;Klothofl/fl mice have significantly higher expression of all bone formation markers analyzed than controls. Second, we found that bone morphology in mice with induced CKD was more affected in mice without Klotho expression in long bones. The phenotypic changes in the skeleton of CKD mice were consistent with rickets/osteomalacia, but the long bones of Prx1cre;Klothofl/fl mice with CKD were significantly more compromised than those of controls. Also, CKD Prx1cre;Klothofl/fl mice did not exhibit the expected increase in bone formation markers that was observed in CKD control mice. The results provide new insight into the limb specific role of Klotho.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2014
- Accession Number
- ADA613419
Entities
People
- Beate Lanske
Organizations
- President and Fellows of Harvard College