p53半剂量缺失纠正1,25(OH)2D3缺乏小鼠的骨质疏松OA北大核心CSTPCD

Objective:To explore whether p53 heterozygote attenuates osteoporosis phenotype of 1,25(OH)2D3 deficient mice by enhancing the antioxidant capacity.Methods:The long bones of 10-week-old wild type(WT)mice,p53 heterozygote(p53+/-)mice,1α-hydroxylase knockout[1α(OH)ase-/-]mice,and 1α(OH)ase-/-p53+/-mice,fed on a high-calcium and high-phosphorus diet,were analyzed and compared using X-ray,micro-CT,histopathological and molecular biology methods to observe and compare changes in serum levels,bone mineralization,bone formation,bone absorption,and oxidative stress expression.Results:Compared with WT mice,p53+/-mice showed no significant differences in serum calcium,phosphorus,parathyroid hormone(PTH),and 1,25(OH)2D3 levels,but had the increased bone density,total collagen(T-col)positive area,osteoblast number,alkaline phosphatase(ALP),and typeⅠcollagen(col-Ⅰ)positive area,along with the decreased levels of reactive oxygen species and the increased expression of the antioxidant enzyme SOD1.Compared with 1α(OH)ase-/-mice,1α(OH)ase-/-p53+/-mice showed no significant differences in serum calcium,phosphorus,and PTH levels,with undetectable levels of 1,25(OH)2D3 in the serum,but showed significantly increased bone density,T-col positive area,osteoblast number,ALP and Col-Ⅰpositive area,decreased osteoclast number and reactive oxygen species levels,and increased expression of SOD1.Conclusion:Half-dose deletion of p53 can attenuate osteoporosis phenotype of 1,25(OH)2D3 deficient mice by enhancing the antioxidant capacity.