Vitamin K Supplementation Modulates Bone Metabolism and Ultra-Structure of Ovariectomized Mice

Abstract

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. Methods: 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. Results: 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. Conclusion: 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.

The Dual Role of Vitamin K2 in “Bone-Vascular Crosstalk”: Opposite Effects on Bone Loss and Vascular Calcification

“…In a model of osteoporotic ovariectomized (OVX) mice, Rangel and collaborators [94] demonstrated how this compound was able to improve BMD and bone formation markers, while decreasing bone resorption markers. Similar results were recently obtained in a model of osteopenic rats, which were characterized by an increase of bone formation and cOC serum levels following MK-4 treatment [95].…”

Zinc Silicate/Nano-Hydroxyapatite/Collagen Scaffolds Promote Angiogenesis and Bone Regeneration via the p38 MAPK Pathway in Activated Monocytes

“…After adding liquid nitrogen into the mortar, the bone tissue was ground into powder. Liquid nitrogen was added continuously . Total cellular RNA was extracted from the tissues using Trizol Reagent (Invitrogen) according to the manufacturer’s instructions, and cDNA was synthesized using 1 μg of RNA and the Revert Aid First Strand cDNA Synthesis Kit (TaKaRa, Dalian, China).…”

“…Liquid nitrogen was added continuously. 25 Total cellular RNA was extracted from the tissues using Trizol Reagent (Invitrogen) according to the manufacturer's instructions, and cDNA was synthesized using 1 μg of RNA and the Revert Aid First Strand cDNA Synthesis Kit (TaKaRa, Dalian, China). Quantitative real-time reverse-transcriptase polymerase chain reaction (qRT-PCR) analyses were performed in triplicate using the SYBR Premix Ex TaqTM kit (TaKaRa, Dalian, China) and assessed using Bio-Rad X97 System software.…”

Vitamin K and Osteoporosis

“…Wu et al showed that both PK and MK (MK-4 and MK-7) inhibitor osteoclast-mediated effects on bone resorption in a dose dependent manner [64]. Furthermore, Rangel et al demonstrated increased compact bone mass, increased bone formation markers and decreased bone resorption markers in ovariectomized (OVX) mice supplemented with Vitamin K [65]. Also, the effect of coadministration of vitamin K2 and other antiosteoporotic drugs, such as Teriparatide [66] and bisphosphonates, has been investigated [21].…”