To determine whether disruption of the p53 gene leads to preservation of trabecular bone volume (BV) after limb immobilisation.
Tibias of immobilised hind limbs of p53 gene knockout (p53(-/-)) and wild-type (p53(+/+)) mice were compared. Right knee joints of 8 week old mice were immobilised in full extension for 7 days. Trabecular structure and bone formation were similar in the p53(-/-) and p53(+/+) control groups.
Immobilisation significantly reduced BV to 77% of the control in p53(+/+) mice, but no change was noted in p53(-/-) mice. After immobilisation, bone formation rate was significantly reduced in p53(+/+) but not in p53(-/-) mice. In bone marrow cell cultures the numbers of alkaline phosphatase positive colony forming units-fibroblastic and mineralised nodules were significantly reduced by immobilisation in p53(+/+) but not in p53(-/-) mice. Immobilisation enhanced p53 mRNA expression in marrow cells of p53(+/+) mice and increased terminal dUTP nick end labelling positive osteocytes and marrow cells in p53(+/+) but not in p53(-/-) mice. Lack of p53 in immobilised mice was associated with preservation of trabecular bone mass and bone formation and suppression of significant apoptosis of marrow cells.
Disruption of the p53 gene preserves trabecular bone mass and leads to bone formation after limb immobilisation.