title: Effect of vitamin K2 on the development of stress-induced osteopenia in a growing senescence-accelerated mouse prone 6 strain.
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.
authors.affiliation: Department of Public Health, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Katsuyama
authors.affiliation: Department of Public Health, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan ; Department of Oral Pathology and Medicine, Okayama University School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
authors.forename: Shigeko
authors.initials: S
authors.lastname: Fushimi
authors.affiliation: Department of Public Health, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Kunikazu
authors.initials: K
authors.lastname: Yamane
authors.affiliation: Department of Natural Sciences, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Department of Obstetrics and Gynecology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Koichiro
authors.initials: K
authors.lastname: Shimoya
authors.affiliation: Department of Medical Toxicology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Toshiko
authors.initials: T
authors.lastname: Okuyama
authors.affiliation: Department of Hygiene, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Midori
authors.initials: M
authors.lastname: Katsuyama
authors.affiliation: Department of Hygiene, Kanazawa University School of Medicine, Kanazawa, Ishikawa 920-8640, Japan.
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Saijoh
authors.affiliation: Department of Medical Toxicology, Kawasaki Medical School, Kurashiki, Okayama 701-0192, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Tomita
keywords: bone formation; bone histomorphometry; bone resorption; senescence-accelerated mouse prone 6; vitamin K2; water-immersion restraint stress