Abstract
Epidemiologic studies showed that higher vitamin K (VK) consumption correlates with a reduced risk of osteoporosis, yet the dispute remains about whether VK is effective in improving bone mineral density (BMD). We sought to discover the anti-osteoporotic effect of menaquinone-4 (MK-4) and evaluate the expression of critical genes related to bone formation and bone resorption pathways in the body. Fifty female C57BL/6 mice (aged 13 weeks) were randomly arranged to a sham-operated group (SHAM, treated with corn oil) and four ovariectomized groups that were administered corn oil (OVX group), estradiol valerate (EV, 2 mg/kg body weight as the positive control), low or high doses of VK (LVK and HVK; 20 and 40 mg MK-4/kg body weight, respectively) by gavage every other day for 12 weeks. Body and uterine weight, serum biochemical indicators, bone microarchitecture, hematoxylin-eosin (HE) staining, and the mRNA expression of critical genes related to bone formation and bone resorption pathways were assessed. Either dose of MK-4 supplementation increased the alkaline phosphatase (ALP), decreased the undercarboxylated osteocalcin (ucOC) and tartrate-resistant acid phosphatase (TRACP, p < 0.05) levels, and presented higher BMD, percent bone volume (BV/TV), trabecular thickness (Tb.Th), and lower trabecular separation (Tb.Sp) and structure model index (SMI, p < 0.05) compared with the OVX group. Additionally, both doses of MK4 increased the mRNA expression of Runx2 and Bmp2 (p < 0.05), whereas the doses down-regulated Pu.1 and Nfatc1 (p < 0.05) mRNA expression, the high dose decreased Osx and Tgfb (p < 0.05) mRNA expression, and the low dose decreased Mitd and Akt1 (p < 0.05) mRNA expression. These data show the dual regulatory effects of MK-4 on bone remodeling in ovariectomized mice: the promotion of bone anabolic activity and inhibition of osteoclast differentiation, which provides a novel idea for treating osteoporosis.
Highlights
Epidemiologic studies showed that higher vitamin K (VK) consumption correlates with a reduced risk of osteoporosis, yet the dispute remains about whether VK is effective in improving bone mineral density (BMD)
Bone homeostasis is a dynamic balance between bone formation mediated by osteoblasts and resorption mediated by osteoclasts under physiological conditions [1]
Mice in the SHAM and OVX groups received the same amount of corn oil, and all treatments were given by gavage every other day for 12 weeks
Summary
Bone homeostasis is a dynamic balance between bone formation mediated by osteoblasts and resorption mediated by osteoclasts under physiological conditions [1]. When the secretion of estrogen decreases or calcium is lacking, it will cause bone loss, low BMD, fragility, which lead to osteoporosis [3]. It threatens the health of middle-aged and the aged, especially postmenopausal women [4]. In preventing and treating osteoporosis, there is an urgent need to seek alternative substances that can simultaneously increase the activity of osteoblasts and inhibit the osteoclastogenesis genes without toxic side effects. Some studies found insufficient evidence for the use of VK supplements to prevent bone loss, fracture, and increase BMD [17,18]. We systematically researched the effects of MK-4 on bone protection and the influences of the MK-4 on expressing critical genes related to bone formation and bone resorption pathways in ovariectomized mice
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
