Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain

Demura

Molecular Medicine Reports

et al. 2017

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The aim of the present study was to determine the molecular basis of the beneficial effects of genistein and/or menaquinone‑4 (MK‑4) on bone quality. Initially, 1 µM genistein was applied to MC3T3‑E1 cells for 24 h and the upregulated mRNAs that were detected by microarray were selected for further examination by reverse transcription‑quantitative‑polymerase chain reaction. Among them, alterations were observed in the level of GATA‑binding protein 6 (GATA6), Notch gene homolog 2 (NOTCH2), Wnt family member 5A (WNT5A), bone γ‑carboxyglutamate protein (BGLAP), chondroadherin (CHAD), dipeptidyl peptidase 4 (DPP4), ectonucleotide pyrophosphatase/phosphodiesterase 2 (ENPP2), alkaline phosphatase (ALP) 3 and ATPase phospholipid‑transporting 11A (ATP11A) in response to treatment with 0.1 µM 17‑β‑estradiol, 1 µM genistein, and/or 1 µM MK‑4. GATA6, NOTCH2 and WNT5A are considered to be associated with osteoclast, but not osteoblast, function; however, increases in osteoblastic mRNAs, including BGLAP and CHAD, were observed in each of the treatment groups at 48 h. Immunocytochemical analysis confirmed an increase in CHAD and DPP4 proteins following the administration of genistein + MK‑4. Furthermore, genistein + MK‑4 led to alterations in cell morphology to spindle or oval shapes, and increased the intensity of ALP staining. Although the level of ALP mRNA was not consistently altered in response to the treatments, a marked increase in ALP activity was observed following 96 h treatment with genistein + MK‑4. Therefore, the simultaneous intake of genistein and MK‑4 appears to be beneficial for the maintenance of bone quality.

Section: ------------------------------------------------------------contrasting

confidence: 55%

Genistein and menaquinone-4 treatment-induced alterations in the expression of mRNAs and their products are beneficial to osteoblastic MC3T3-E1 cell functions

Demura

Molecular Medicine Reports

et al. 2017

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“…VK2 is a fat-soluble vitamin that is important for human health. Recently, studies have identified various physiological effects possessed by VK2, including glycemic control, anti-vascular calcification, lipid-lowering ability, etc. , Otherwise, numerous reports indicated that VK2 plays a vital role in osteoporosis. − Nevertheless, the mechanism of VK2 in T2DOP has not been fully elucidated. Dragh et al found that VK2 is critical in restoring mitochondrial function .…”

Section: Discussionmentioning

confidence: 99%

A Novel Anti-Osteoporosis Mechanism of VK2: Interfering with Ferroptosis via AMPK/SIRT1 Pathway in Type 2 Diabetic Osteoporosis

Jin

Tan

Yao

et al. 2023

J. Agric. Food Chem.

Type 2 diabetic osteoporosis (T2DOP) is a chronic bone metabolic disease. Compared with traditional menopausal osteoporosis, the long-term high glucose (HG) microenvironment increases patients’ risk of fracture and osteonecrosis. We were accumulating evidence that implicated ferroptosis as a pivotal mechanism of glucolipotoxicity-mediated death of osteocytes and osteoblast, a novel form of programmed cell death resulting from uncontrolled lipid peroxidation depending on iron. Vitamin K2 (VK2), a fat-soluble vitamin, is clinically applied to prevent osteoporosis and improve coagulation. This study aimed to clarify the role and mechanism of VK2 in HG-mediated ferroptosis. We established the mouse T2DOP model by intraperitoneal injection of streptozotocin solution and a high-fat and high-sugar diet. We also cultured bone marrow mesenchymal stem cells (BMSCs) in HG to simulate the diabetic environment in vitro. Based on our data, VK2 inhibited HG-mediated bone loss and ferroptosis, the latter manifested by decreased levels of mitochondrial reactive oxygen species, lipid peroxidation, and malondialdehyde and increased glutathione in vitro. In addition, VK2 treatment was capable of restoring bone mass and strengthening the expression of SIRT1, GPX4, and osteogenic markers in the distal femurs. As for further mechanism exploration, we found that VK2 could activate AMPK/SIRT1 signaling, and knockdown of SIRT1 by siRNA prevented the VK2-mediated positive effect in HG-cultured BMSCs. Summarily, VK2 could ameliorate T2DOP through the activation of the AMPK/SIRT1 signaling pathway to inhibit ferroptosis.

“…The mice were then divided into two groups: WRS ( n = 8) and control ( n = 8) groups. The WRS method has been previously described in detail [ 9 , 11 , 13 , 14 ]. Briefly, mice were restrained in a 50-mL conical centrifuge tube with multiple punctures and vertically immersed in the xiphoid process in a 24 °C ± 1 °C water bath for 6 h per day, five times per week, for four weeks.…”

Section: Methodsmentioning

confidence: 99%

“…Water-immersion restraint stress (WRS) is a well-characterized chronic stress model. WRS in a mouse model results in diminished BMD [ 9 ], altered tryptophan catabolism [ 10 ], gastric damage [ 11 ], and sleep disturbances [ 12 ]. However, analyzing the impact of repetitive or chronic stress can be challenging, as inbred mice strains frequently become habituated to a given set of experimental conditions.…”

Section: Introductionmentioning

confidence: 99%

Chronic Stress Induces Type 2b Skeletal Muscle Atrophy via the Inhibition of mTORC1 Signaling in Mice

2023

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Chronic stress induces psychological and physiological changes that may have negative sequelae for health and well-being. In this study, the skeletal muscles of male C57BL/6 mice subjected to repetitive water-immersion restraint stress to model chronic stress were examined. In chronically stressed mice, serum corticosterone levels significantly increased, whereas thymus volume and bone mineral density decreased. Further, body weight, skeletal muscle mass, and grip strength were significantly decreased. Histochemical analysis of the soleus muscles revealed a significant decrease in the cross-sectional area of type 2b muscle fibers. Although type 2a fibers also tended to decrease, chronic stress had no impact on type 1 muscle fibers. Chronic stress increased the expression of REDD1, FoxO1, FoxO3, KLF15, Atrogin1, and FKBP5, but did not affect the expression of myostatin or myogenin. In contrast, chronic stress resulted in a decrease in p-S6 and p-4E-BP1 levels in the soleus muscle. Taken together, these results indicate that chronic stress promotes muscle atrophy by inhibiting mammalian targets of rapamycin complex 1 activity due to the upregulation of its inhibitor, REDD1.