Inhibitory effect of menaquinone‐7 (vitamin K2) on osteoclast‐like cell formation and osteoclastic bone resorption in rat bone tissues in vitro

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• 作者：Yamaguchi ; Masayoshi ; Ma ; Zhong Jie
• 关键词：menaquinone ; 7 ; vitamin K2 ; osteoclast ; bone resorption
• 刊名：Molecular and Cellular Biochemistry
• 出版时间：2001
• 出版年：2001
• 期刊代码：38_03008177
• 类别：cp
• 卷：228
• 期：1/2
• 页码：39-47
• 数据来源：sp

摘要

The effect of menaquinone‐7 (MK‐7; vitamin K$\_2$) on oateoclast‐like cell formation and osteoclastic bone resorption in rat femoral tissues in vitro was investigated. The bone marrow cells were cultured for 7 days in a &agr;‐minimal essential medium (&agr;‐MEM) containing a well‐known bone resorbing agent [parathyroid hormone (1–34) (PTH) or prostaglandin E$\_2$ (PGE$\_2$)] with an effective concentration. Osteoclast‐like cells were estimated by staining for tartrate‐resistant acid phosphatase (TRACP), a marker enzyme of osteoclasts. The presence of PTH (10$^–8$ M) or PGE$\_2$ (10$^–6$ M) induced a remarkable increase in osteoclast‐like multinucleated cells. These increases were significantly inhibited by MK‐7 (10$^–8$–10$^–5$ M). MK‐7 (10$^–7$ and 10$^–6$ M) significantly inhibited phorbol 12‐myristate 13‐acetate‐induced osteoclast‐like cell formation, whereas MK‐7 did not inhibit dibutyryl cyclic adenosine monophosphate (DcAMP) (10$^–5$ M)‐induced osteoclast‐like cell formation. These results suggest that the inhibitory action of MK‐7 is partly involved in protein kinase C signaling. The bone cells isolated from rat femoral tissues were cultured for 48 h in an &agr;‐MEM containing either vehicle or MK‐7 (10$^–8$–10$^–5$ M). The presence of MK‐7 (10$^–6$ and 10$^–5$ M) caused a significant decrease in the number of mature osteoclasts. Such a decrease was also seen in the presence of calcitonin (10$^–10$–10$^–8$ M), DcAMP (10$^–6$ and 10$^–5$ M), or calcium chloride (10$^–3$ and 10$^–3$ M). The effect of MK‐7 (10$^–6$ M) in decreasing the number of osteoclasts was not further enhanced in the presence of calcitonin (10$^–8$ M), DcAMP (10$^–5$M), or calcium chloride (10$^–3$ M), and was completely abolished by the presence of dibucaine (10$^–6$ M) or staurosporine (10$^–7$ M), which are inhibitors of Ca$^2+$‐dependent protein kinases. These results suggested that MK‐7 has a suppressive effect on osteoclasts. Moreover, the femoral‐metaphyseal tissues obtained from rats were cultured for 48 h in Dulbecco's modified Eagle's medium containing either vehicle, PTH (10$^–7$ M), or PGE$\_2$ (10$^–5$ M) in the absence or presence of MK‐7 (10$^–7$–10$^–5$ M). The presence of PTH or PGE$\_2$ induced a significant decrease in bone calcium content. These decreases were significantly blocked by MK‐7 (10$^–7$–10$^–5$ M). This study demonstrates that MK‐7 has an inhibitory effect on osteoclastic bone resorption in vitro.