p53 functions as a negative regulator of osteoblastogenesis, osteoblast-dependent osteoclastogenesis, and bone remodeling
2006
p53 is a well known tumor suppressor. We show that p53 also regulates osteoblast
differentiation, bone formation, and osteoblast-dependent osteoclast differentiation.
Indeed,
p53 − / − mice display a high bone mass phenotype, and
p53 − / − osteoblasts show accelerated differentiation, secondary to an increase in expression of
the osteoblast differentiation factor osterix, as a result. Reporter assays indicate that
p53 represses osterix transcription by the minimal promoter in a
DNA-binding–independent manner. In addition,
p53 − / − osteoblasts have an enhanced ability to favor osteoclast differentiation, in association
with an increase in expression of macrophage-colony stimulating factor, which is under the
control of osterix. Furthermore, inactivating p53 is sufficient to rescue the osteoblast
differentiation defects observed in mice lacking c-Abl, a p53-interacting protein. Thus,
these results identify p53 as a novel regulator of osteoblast differentiation,
osteoblast-dependent osteoclastogenesis, and bone remodeling.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
54
References
203
Citations
NaN
KQI