Department of Oral and Maxillofacial Reconstructive Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Sikata-cho, Okayama City, 7008525, Japan.
Osteoporos Int. 2010 Aug;21(8):1437-47. doi: 10.1007/s00198-009-1075-y. Epub 2009 Oct 8.
The main component of the metabolic by-products of fermentation by Propionibacterium freudenreichii ET-3 is 1,4-dihydroxy-2-naphthoic acid (DHNA), which has a naphthoquinone skeleton, as in vitamin K2. This study showed that DHNA improved bone mass reduction with osteoporosis model mice caused by FK506.
Growth of the intestinal bacterium Lactobacillus bifidus is specifically facilitated by DHNA. The present study used osteoporosis model mice to investigate the effects of DHNA on bone remodeling.
FK506, an immunosuppressant, was used to prepare osteoporosis model mice. Thirty mice were divided into three groups: FK group, FK+DHNA group, and control group. In the FK group, FK506 was administered to induce bone mass reduction. In the FK-DHNA group, FK506 and DHNA were administered concurrently to observe improvements in bone mass reduction. To ascertain systemic and local effects of DHNA, we investigated systemic pathological changes in colon, kidney function and cytokine dynamics, and morphological and organic changes in bone and osteoclast dynamics as assessed by culture experiments.
Compared to the FK group without DHNA, colon damage and kidney dysfunction were milder for FK+DHNA group, and production of inflammatory cytokines (interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha) was more suppressed. Furthermore, compared to the group without DHNA, histological analyses and radiography showed that bone resorption was suppressed for the DHNA group. Culture experiments using osteoclasts from murine bone marrow showed osteoclast suppression for the DHNA group compared to the group without DHNA.
These results show that DHNA has some effects for improving bone mass reduction caused by FK506.
丙酸杆菌 ET-3 发酵代谢产物的主要成分是 1,4-二羟基-2-萘甲酸（DHNA），它具有萘醌骨架，与维生素 K2 相似。本研究表明，DHNA 可改善 FK506 引起的骨质疏松症模型小鼠的骨量减少。
DHNA 特异性促进肠道细菌双歧杆菌的生长。本研究使用骨质疏松症模型小鼠研究 DHNA 对骨重塑的影响。
使用免疫抑制剂 FK506 制备骨质疏松症模型小鼠。将 30 只小鼠分为 3 组：FK 组、FK+DHNA 组和对照组。FK 组给予 FK506 诱导骨量减少。FK-DHNA 组同时给予 FK506 和 DHNA，观察骨量减少的改善情况。为了确定 DHNA 的全身和局部作用，我们通过培养实验研究了 DHNA 对结肠、肾功能和细胞因子动力学的全身和局部影响，以及对骨和破骨细胞动力学的形态和有机变化。
与未用 DHNA 的 FK 组相比，FK+DHNA 组的结肠损伤和肾功能障碍较轻，炎症细胞因子（白细胞介素 (IL)-1β、IL-6 和肿瘤坏死因子 (TNF)-α）的产生受到更抑制。此外，与未用 DHNA 的组相比，组织学分析和 X 射线照相显示，DHNA 组的骨吸收受到抑制。来自鼠骨髓的破骨细胞的培养实验显示，DHNA 组的破骨细胞受到抑制，与未用 DHNA 的组相比。
这些结果表明，DHNA 对改善 FK506 引起的骨量减少有一定作用。
