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度骨化醇可减轻衰老小鼠的骨质退化和软骨退变。

Doxercalciferol Alleviates Bone Deteriorations and Cartilage Degeneration in Aging Mice.

作者信息

Li Jian, Li Nan, Yan Shuangtong, Liu Minyan, Sun Banruo, Lu Yanhui, Shao Yinghong

机构信息

Department of Geriatric Endocrinology, Chinese PLA General Hospital, National Clinical Center of Geriatric Medicine, Beijing, China.

Department of Outpatient, Chinese PLA General Hospital, Beijing, China.

出版信息

Exp Clin Endocrinol Diabetes. 2020 Aug;128(8):540-547. doi: 10.1055/a-0754-1956. Epub 2018 Oct 31.

Abstract

BACKGROUND

Age-related bone deteriorations are the common endocrine disorders in the elderly population, leading to an increased risk of fractures. Therefore, effective treatment strategies provide a way to prevent bone loss and improve the quality of life in the elderly population. The present study aimed to investigate the anti-osteoporotic effects of doxercalciferol (DOX) in aging mice.

METHODS

Bone metabolism-related markers were measured by ELISA assay. The expression of bone formation and resorption-related genes was performed by RT-qPCR analysis. Hematoxylin and eosin (H&E) and Safranin O staining were performed to analyze the trabecular bone and cartilage degeneration.

RESULTS

Aging resulted in urine ca excretion, a decrease in bone ca content and reduction of biomechanical strength in mice. We also found that the level of PTH was increased in aging mice, while DOX administration markedly down-regulated serum PTH in aging mice. H&E and Safranin O staining showed that DOX protected against aging-induced bone loss and cartilage regeneration in the tibia from aging mice. Furthermore, DOX treatment resulted in an increase in and mRNA expression and a decrease in Ctsk, MMP-9 and mRNA expression in the tibia from aging mice.

CONCLUSION

These findings indicated that DOX had a beneficial effect on age-related bone deteriorations in aging mice by promoting osteoblast activity and cartilage regeneration and inhibiting osteoclast-specific genes expression.

摘要

背景

与年龄相关的骨质退化是老年人群常见的内分泌疾病,会导致骨折风险增加。因此,有效的治疗策略为预防老年人骨质流失和提高生活质量提供了途径。本研究旨在探讨多西骨化醇(DOX)对衰老小鼠的抗骨质疏松作用。

方法

通过酶联免疫吸附测定(ELISA)法检测骨代谢相关标志物。通过逆转录定量聚合酶链反应(RT-qPCR)分析检测骨形成和骨吸收相关基因的表达。进行苏木精-伊红(H&E)染色和番红O染色以分析小梁骨和软骨退变情况。

结果

衰老导致小鼠尿钙排泄增加、骨钙含量降低以及生物力学强度下降。我们还发现衰老小鼠甲状旁腺激素(PTH)水平升高,而给予DOX可显著下调衰老小鼠血清PTH水平。H&E染色和番红O染色显示,DOX可防止衰老小鼠胫骨出现衰老诱导的骨质流失和软骨再生。此外,DOX处理导致衰老小鼠胫骨中 和 信使核糖核酸(mRNA)表达增加,而组织蛋白酶K(Ctsk)、基质金属蛋白酶9(MMP-9)和 mRNA表达降低。

结论

这些研究结果表明,DOX通过促进成骨细胞活性和软骨再生以及抑制破骨细胞特异性基因表达,对衰老小鼠与年龄相关的骨质退化具有有益作用。

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