p53通过增强抗氧化纠正1,25(OH)2D3缺乏所致骨质疏松
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1.南京医科大学康达学院;2.南京医科大学附属宿迁第一人民医院

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宿迁市科技计划自然科学基金项目(K202001);江苏省高等学校基础科学(自然科学)研究面上项目(22KJB320016);南京医科大学康达学院科研人才培养计划(KD2021KYRC025);宿迁市科技计划资助(KY202214);


p53 heterozygote attenuates osteoporosis phenotype of 1,25(OH)2D3 deficiency mice by enhancing the antioxidant capacity
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    摘要:

    目的:探索p53半剂量缺失通过增强抗氧化能力纠正活性维生素D缺乏所致的骨质疏松。方法:取10周龄高钙高磷饮食喂养的同窝野生型(wild type, WT)小鼠、p53半剂量缺失杂合子(p53+/-)小鼠、1α羟化酶基因敲除(1α(OH)ase-/-)小鼠及p53半剂量缺失的1α羟化酶基因敲除(1α(OH)ase-/-p53+/-)小鼠的长骨,利用x线、CT、组织病理学和分子生物学等方法观察比较了各组小鼠血清学、长骨骨矿化、骨形成、骨吸收以及氧化应激等表达变化。结果:与WT小鼠相比,p53+/-小鼠血清钙、磷、甲状旁腺素(Parathyroid hormone , PTH)和1,25(OH)2D3水平无明显差异,骨密度、总胶原(Total Collagen, T-col)阳性面积、成骨细胞数量、碱性磷酸酶(alkaline phosphatase, ALP)和Ⅰ型胶原(Collagen type I, Col-I)阳性面积均有所增加,活性氧水平降低,抗氧化酶SOD1表达增加。与1α(OH)ase-/-小鼠相比,1α(OH)ase-/-p53+/-小鼠血清钙、磷和PTH无明显差异,血清中检测不到1,25(OH)2D3,骨密度、T-col、成骨细胞数量、ALP和Col-I阳性面积均明显增加,破骨细胞数量、活性氧水平降低,抗氧化酶SOD1表达增加。结论:p53半剂量缺失能够通过增强抗氧化能力纠正活性维生素D缺乏所致的骨质疏松。

    Abstract:

    Objective: To explore whether p53 heterozygote could attenuate osteoporosis phenotype of 1,25(OH)2D3 deficiency mice by enhancing the antioxidant capacity. Methods: The long bones of 10-week-old p53 heterozygote (p53+/-) mice, 1α-hydroxylase knockout (1α(OH)ase-/-) mice, 1α(OH)ase-/-p53+/- mice and WT (wild type, WT) littermates fed on a high calcium and phosphorus diet were analyzed and compared each other using x-ray, CT, histopathological and molecular techniquesto observe phenotype and alterations of bone density, bone formation, bone absorption and oxidative stress of these mice. Results: Compared with WT littermates, serum levels of calcium, phosphorus, parathyroid hormone (PTH) and 1,25(OH)2D3 were not altered in p53+/- mice. Bone density, total collagen (T-col) positive area, the number of osteoblast, alkaline phosphatase (ALP) and collagen type I (Col-Ⅰ) positive area were increased slightly in p53+/- mice. ROS levels were decreased, and SOD1 protein expression levels were increased in p53+/- mice. In 1α(OH)ase-/- and 1α(OH)ase-/-p53+/- mice, serum levels of calcium, phosphorus and PTH levels were normal and 1,25(OH)2D3 levels were undetectable. Compared with 1α(OH)ase-/- mice, bone density, T-col positive area, the number of osteoblast, ALP positive area and Col-I positive area of 1α(OH)ase-/-p53+/- mice were increased clearly. The number of osteoclast and ROS levels were decreased while SOD1 protein expression levels were increased in 1α(OH)ase-/-p53+/- mice. Conclusion: p53 heterozygote can attenuate osteoporosis phenotype of 1,25(OH)2D3 deficiency mice by enhancing the antioxidant capacity.

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  • 收稿日期:2023-10-25
  • 最后修改日期:2023-11-21
  • 录用日期:2023-11-27
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