Rangel Letícia Batista Azevedo, de Siqueira Daniel, Soares Olívia do Rosário, Santana Higor Scardini, Miguel Emílio de Castro, da Cunha Maura, Oliveira Andre Lacerda de Abreu, Pedrosa Diego França, Resgala Ludmilla Carvalho Rangel, Neto Helder Azevedo Rangel, Gomes-Rochette Neuza Felix, Eis Sérgio Ragi, Graceli Jones Bernardes, Silva Ian Victor
Aging Cell Biology Laboratory, Department of Morphology, UFES, Vitória, Brazil.
Programa de Pós Graduação em Biotecnologia (UFES/RENORBIO), Health Sciences Center, UFES, Vitória, Brazil.
Cell Physiol Biochem. 2018;51(1):356-374. doi: 10.1159/000495234. Epub 2018 Nov 19.
BACKGROUND/AIMS: Osteoporosis is a bone metabolic disease that affects mostly post-menopausal women. There has been shown that vitamin K (VK) supplementation during menopause may decrease bone loss as well as risk of bone breaking. Aiming to clarify the beneficial role of VK in bone metabolism during menopause, we investigated mineral metabolism and bone ultrastructure of ovariectomized (OVX) mice.
To determine the effects chronic use of VK in bone structure and mineral metabolism in OVX mice, we used several methods, such as DXA, µCTScan, and SEM as well as biomolecular techniques, such as ELISA and qRT-PCR. In addition, complete analysis of serum hormonal and other molecules associated to bone and lipid metabolism were evaluated overview the effects of VK in menopause murine model.
VK treatment significantly affects Pi metabolism independently of OVX, changing Pi plasma, urinary output, balance, and Pi bone mass. Interestingly, VK also increased VLDL in mice independently of castration. In addition, VK increased compact bone mass in OVX mice when we evaluated it by DXA, histomorphometry, µCTScanning. VK increased bone formation markers, osteocalcin, HYP- osteocalcin, and AP whereas it decreased bone resorption markers, such as urinary DPD/creatinine ratio and plasmatic TRAP. Surprisingly, SEM images revealed that VK treatment led to amelioration of microfractures observed in OVX untreated controls. In addition, SHAM operated VK treated mice exhibited higher number of migrating osteoblasts and in situ secretion of AP. OVX led to decreased to in situ secretion of AP that was restored by VK treatment. Moreover, VK treatment increased mRNA expression of bone Calbindin 28KDa independently of OVX.
VK treatment in OVX mice exhibited beneficial effects on bone ultrastructure, mostly by altering osteoblastic function and secretion of organic bone matrix. Therefore, VK could be useful to treat osteopenic/osteoporotic patients.
背景/目的：骨质疏松症是一种主要影响绝经后女性的骨代谢疾病。研究表明，绝经期间补充维生素K（VK）可能会减少骨质流失以及骨折风险。为了阐明VK在绝经期间骨代谢中的有益作用，我们研究了去卵巢（OVX）小鼠的矿物质代谢和骨超微结构。
为了确定长期使用VK对OVX小鼠骨骼结构和矿物质代谢的影响，我们使用了多种方法，如双能X线吸收法（DXA）、显微计算机断层扫描（µCTScan）和扫描电子显微镜（SEM），以及生物分子技术，如酶联免疫吸附测定（ELISA）和定量逆转录聚合酶链反应（qRT-PCR）。此外，全面分析了与骨和脂质代谢相关的血清激素及其他分子，以评估VK对绝经小鼠模型的影响。
VK治疗显著影响磷（Pi）代谢，与OVX无关，改变了血浆Pi、尿排出量、平衡和骨Pi质量。有趣的是，VK还独立于去势增加了小鼠极低密度脂蛋白（VLDL）。此外，当我们通过DXA、组织形态计量学、µCT扫描评估时，VK增加了OVX小鼠的密质骨质量。VK增加了骨形成标志物骨钙素、Hyp-骨钙素和碱性磷酸酶（AP），而降低了骨吸收标志物，如尿脱氧吡啶啉/肌酐比值和血浆抗酒石酸酸性磷酸酶（TRAP）。令人惊讶的是，SEM图像显示VK治疗可改善未治疗的OVX对照中观察到的微骨折。此外，假手术的VK治疗小鼠表现出更多迁移的成骨细胞和AP的原位分泌。OVX导致AP原位分泌减少，而VK治疗可恢复。此外，VK治疗独立于OVX增加了骨钙结合蛋白28KDa的mRNA表达。
VK治疗对OVX小鼠的骨超微结构具有有益作用，主要是通过改变成骨细胞功能和有机骨基质的分泌。因此，VK可能对治疗骨质减少/骨质疏松患者有用。
