Abstract
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.
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Figure 1 .
p53 mRNA expression in bone marrow cells. Representative data are shown. C, control; IM, immobilised group.
Figure 2 .
TUNEL staining of the trabecular bone of (A) p53+/+ and (B) p53-/- mice obtained at 7 days after immobilisation. Arrows indicate TUNEL positive osteocytes. Scale bar = 50 µm. Each tissue section was finally counterstained with haematoxylin and eosin. (C) Proportion of TUNEL positive bone marrow cells. Data are mean (SD) values of five mice. *p<0.05 v p53+/++C; +p<0.05 v p53+/++IM, by the Mann-Whitney U test. The values of p53-/-+C are not significantly different from those for p53+/++C and the values of p53-/-+IM are not significantly different from those for p53-/-+C.