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

Katsuyama,Hironobu; Fushimi,Shigeko; Yamane,Kunikazu; Watanabe,Yoko; Shimoya,Koichiro; Okuyama,Toshiko; Katsuyama,Midori; Saijoh,Kiyofumi; Tomita,Masafumi

doi:10.3892/etm.2015.2621

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

Authors:
- Hironobu Katsuyama
- Shigeko Fushimi
- Kunikazu Yamane
- Yoko Watanabe
- Koichiro Shimoya
- Toshiko Okuyama
- Midori Katsuyama
- Kiyofumi Saijoh
- Masafumi Tomita
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Affiliations: Department of Public Health, Kawasaki Medical School, Kurashiki, Okayama 701‑0192, Japan, Department of Natural Sciences, Kawasaki Medical School, Kurashiki, Okayama 701‑0192, Japan, Department of Obstetrics and Gynecology, Kawasaki Medical School, Kurashiki, Okayama 701‑0192, Japan, Department of Medical Toxicology, Kawasaki Medical School, Kurashiki, Okayama 701‑0192, Japan, Department of Hygiene, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920‑8640, Japan
Published online on: July 7, 2015 https://doi.org/10.3892/etm.2015.2621
Pages: 843-850
Copyright: © Katsuyama et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Vitamin K2 (VK2) has been used as a therapeutic agent for osteoporosis, since it has been suggested to be able to reduce the frequency of fractures by improving bone quality; however, bone turnover is strictly regulated by various cytokines and hormones. In the present study, the effect of menaquinone‑4 (MK‑4) on bone turnover was investigated using the senescence‑accelerated mouse prone 6 (SAMP6) strain. Since water‑immersion restraint stress (WRS) causes a significant decrease in bone mineral density (BMD), WRS was used as the bone resorption model in the SAMP6 strain. Six‑week‑old SAMP6 male mice were divided into the following three groups: Control, WRS and WRS + MK‑4. WRS was performed for 6 h per day, 5 times a week, for 4 weeks. Following WRS, MK‑4 (30 mg/kg) was injected subcutaneously 3 times a week for 4 weeks. No growth retardation was observed in the WRS groups as compared with the control group. In the WRS groups, the BMD was significantly lower than that in the control group. The levels of bone formation and resorption markers were increased in the WRS groups, indicating that WRS reduced the BMD by promoting high bone turnover. A bone histomorphometrical examination showed that the trabecular (Tb) bone mass in the secondary spongiosa at the distal femur was significantly reduced in the WRS mice, and this reduction was abrogated by MK‑4 treatment. Specifically, the Tb bone reduction was caused by the activation of osteoclasts (Ocs), and Oc activity was suppressed by MK‑4. The number of osteoblasts and the mineral apposition rate were significantly increased in the WRS and WRS + MK‑4 mice, suggesting that WRS triggered a significantly higher mineral apposition rate. These results indicate that MK‑4 can induce recovery from the bone mineral loss caused by WRS treatment. Further studies are required to clarify the association between bone quality and MK‑4.

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