Big bones in p53 mutants

On page 115, a famous tumor suppressor is uncovered as a suppressor of bone development. Wang et al. show that p53 curbs bone growth by inhibiting osteoblast differentiation and proliferation.Mice deficient in p53 have a high incidence of tumor formation and often die prematurely from lymphomas. Few developmental abnormalities had been found, however. The authors suspected a bone defect might exist, since they had shown that c-Abl, a kinase that interacts with p53, is required for osteoblast differentiation. By looking beyond bone morphology, they indeed found abnormalities in the p53 mutant skeletons. The deficiencies were able to rescue the differentiation defect of mice lacking c-Abl.

Mice lacking only p53 had increased bone mass. The effects were due to accelerated differentiation of bone-forming osteoblasts. Mutants also had more osteoblasts, suggesting that p53...