Article Text
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.
- apoptosis
- p53
- bone marrow
- colony forming units
- immobilisation
- AP, alkaline phosphatase
- BV, bone volume
- CFU-f, colony forming units-fibroblastic
- RT-PCR, reverse transcriptase-polymerase chain reaction
- TGF, transforming growth factor
- TUNEL, terminal dUTP nick end labelling