Trabecular bone mass and bone formation are preserved after limb immobilisation in p53 null mice

Abstract

Objectives: To determine whether disruption of the p53 gene leads to preservation of trabecular bone volume (BV) after limb immobilisation. Materials and methods: 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. Results: 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. Conclusion: Disruption of the p53 gene preserves trabecular bone mass and leads to bone formation after limb immobilisation.