Department of Orthopaedic Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Osteoporos Int. 2017 Mar;28(3):1063-1075. doi: 10.1007/s00198-016-3830-1. Epub 2016 Nov 28.
Oxygen ultra-fine bubbles (OUB) saline injection prevents bone loss of glucocorti\coid-induced osteoporosis in mice, and OUB inhibit osteoclastogenesis via RANK-TRAF6-c-Fos-NFATc1 signaling and RANK-p38 MAPK signaling in vitro.
Ultra-fine bubbles (<200 nm in diameter) have several unique properties, and they are tested in various medical fields. The purpose of this study was to investigate the effects of oxygen ultra-fine bubbles (OUB) on glucocorticoid-induced osteoporosis (GIO) model mice.
Prednisolone (PSL, 5 mg) was subcutaneously inserted in 6-month-old male C57BL/6J mice, and 200 μl of saline, OUB-diluted saline, or nitrogen ultra-fine bubbles (NUB)-diluted saline was intraperitoneally injected three times per week for 8 weeks the day after operations. Mice were divided into four groups; (1) control, sham-operation + saline; (2) GIO, PSL + saline; (3) GIO + OUB, PSL + OUB saline; (4) GIO + NUB, PSL + NUB saline. The effects of OUB on osteoblasts and osteoclasts were examined by serially diluted OUB medium in vitro.
Bone mass was significantly decreased in GIO [bone volume/total volume (%): control vs. GIO 12.6 vs. 7.9; p < 0.01] while significantly preserved in GIO + OUB (GIO vs. GIO + OUB 7.9 vs. 12.9; p < 0.05). In addition, tartrate-resistant acid phosphatase (TRAP)-positive cells in the distal femur [mean osteoclasts number/bone surface (mm)] was significantly increased in GIO (control vs. GIO 6.8 vs. 11.6; p < 0.01) while suppressed in GIO + OUB (GIO vs. GIO + OUB 11.6 vs. 7.5; p < 0.01). NUB did not affect these parameters. In vitro experiments revealed that OUB significantly inhibited osteoclastogenesis by inhibiting RANK-TRAF6-c-Fos-NFATc1 signaling, RANK-p38 MAPK signaling, and TRAP/Cathepsin K/DC-STAMP mRNA expression in a concentration-dependent manner. OUB did not affect osteoblastogenesis in vitro.
OUB prevent bone loss in GIO mice by inhibiting osteoclastogenesis.
研究氧超细微气泡（OUB）对糖皮质激素诱导骨质疏松症（GIO）模型小鼠的影响。
将 6 月龄雄性 C57BL/6J 小鼠背部皮下注射泼尼松龙（PSL，5mg），术后第 2 天起每周 3 次经腹腔内注射 200μl 生理盐水、OUB 稀释生理盐水或氮超细微气泡（NUB）稀释生理盐水，共 8 周。将小鼠分为 4 组：（1）对照组，假手术+生理盐水；（2）GIO 组，PSL+生理盐水；（3）GIO+OUB 组，PSL+OUB 生理盐水；（4）GIO+NUB 组，PSL+NUB 生理盐水。通过体外连续稀释 OUB 培养基观察 OUB 对成骨细胞和破骨细胞的影响。
GIO 组骨量明显减少[骨体积/总体积（%）：对照组 vs. GIO 为 12.6% vs. 7.9%；p<0.01]，而 GIO+OUB 组则明显增加（GIO 组 vs. GIO+OUB 组为 7.9% vs. 12.9%；p<0.05）。此外，远端股骨 TRAP 阳性细胞[平均破骨细胞数/骨表面（mm）]在 GIO 组明显增加（对照组 vs. GIO 组为 6.8% vs. 11.6%；p<0.01），而在 GIO+OUB 组则受到抑制（GIO 组 vs. GIO+OUB 组为 11.6% vs. 7.5%；p<0.01）。NUB 对这些参数没有影响。体外实验结果显示，OUB 以浓度依赖性方式显著抑制 RANK-TRAF6-c-Fos-NFATc1 信号、RANK-p38 MAPK 信号和 TRAP/Cathepsin K/DC-STAMP mRNA 表达，从而抑制破骨细胞的生成。OUB 对体外成骨细胞的生成没有影响。
OUB 通过抑制破骨细胞生成来预防 GIO 小鼠的骨丢失。
