| First Author | Rasheed N | Year | 2006 |
| Journal | Hum Mol Genet | Volume | 15 |
| Issue | 12 | Pages | 1938-48 |
| PubMed ID | 16644862 | Mgi Jnum | J:112068 |
| Mgi Id | MGI:3655443 | Doi | 10.1093/hmg/ddl116 |
| Citation | Rasheed N, et al. (2006) Atm-deficient mice: an osteoporosis model with defective osteoblast differentiation and increased osteoclastogenesis. Hum Mol Genet 15(12):1938-48 |
| abstractText | Atm is a Ser/Thr kinase involved in DNA damage response and is required for genome integrity and stem cell renewal. Here, we report an additional role for Atm in bone remodeling. Atm-/- mice showed reduced bone mass, especially at the trabecular bones, accompanied by a decrease in bone formation rate and defective differentiation of osteoblasts, but normal numbers of osteoprogenitor cells and osteoblasts. Atm might affect osteoblast differentiation by modulating the expression of osterix, a lineage-specific transcription factor essential for osteoblast maturation, likely via the bone morphogenetic proteins pathway. Atm-/- mice also displayed a marked increase in osteoclastogenesis and bone resorption, although Atm had no cell-autonomous effect on osteoclast differentiation and resorption. Increased osteoclastogenesis could be caused by a substantial reduction in testosterone and estradiol levels in male and female mice, respectively. The steroid hormone deficiency is a result of gonad developmental defects, which led to an increase in serum gonadotrophic hormone, FSH via a feedback regulation. Overall, these results indicate that Atm deficiency leads to osteoporosis mainly as a result of hypogonadism-induced bone resorption together with compromised osteoblast differentiation, and that Atm plays a positive role in regulating expression of osteoblast-specific transcription factor, osterix. |
