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

¹ Department of Radiation Biology and Health, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
² Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan

Correspondence to:
Correspondence to:
Dr A Sakai
Department of Orthopaedic Surgery, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan; a-sakai{at}med.uoeh-u.ac.jp

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.

Keywords: apoptosis; p53; bone marrow; colony forming units; immobilisation

Abbreviations: 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