Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect
Effect of Locally Applied Fluvastatin in Low-turnover Osteoporosis Model Mouse with Femur Bone Defect
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DOI：
10.2485/jhtb.24.147
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发表时间：
2015-04-01
影响因子：
0.4
通讯作者：
Yajima, Yasutomo
中科院分区：
文献类型：
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作者：
Ohira, Takashi;Tanabe, Koji;Yajima, Yasutomo
本研究的目的是研究局部施用氟伐他汀-明胶复合物对低转换骨质疏松症小鼠骨缺损愈合的影响。明胶被用作氟伐他汀的载体。通过将每种浓度的氟伐他汀溶解在75 mg/mL明胶溶液中来制备氟伐他汀-明胶复合物溶液。将明胶溶液与空气混合，然后冻干1天并通过干热交联以制备氟伐他汀-明胶复合物海绵。交联后，将复合海绵切成直径为1 mm、高为1 mm的碎片，以适应骨缺损区域。将海绵中氟伐他汀的量调节至对照（0 nmol）、0.1 nmol、0.2 nmol和0.4 nmol。采用20周龄低转换骨质疏松模型小鼠（SAMP 6）和正常模型小鼠（SAMR 1），在股骨远端两侧各1 mm或3 mm处，分别制作直径和深度为1.0 mm的圆柱形和骨缺损。然后将复合海绵插入每个部位，并闭合伤口。然后进行放射学分析和组织学检查。在SAMP 6中，0.1nmol和0.2nmol组骨缺损区的骨体积在14和21天时显著高于对照组和0.4nmol组。组织学观察显示，0.1nmol和0.2nmol组在14和21天新生骨体积比对照组和0.4nmol组增加。SAMR 1组新生骨体积大于SAMP 6组，SAMP 6组与SAMR 1组氟伐他汀的最适浓度不同。本研究表明，局部给予氟伐他汀-明胶复合物海绵可改善低转换型骨质疏松症的骨愈合。
The aim of this study was to investigate the effects of local administration of fluvastatin-gelatin complex on the healing of bone defects in low-turnover osteoporosis mice. Gelatin was used as a carrier of the fluvastatin. A fluvastatin-gelatin complex solution was created by dissolving each concentration of fluvastatin in a 75mg/mL gelatin solution. The gelatin solution was mixed with air, then lyophilized for 1 day and crosslinked by dry heating to make a fluvastatin-gelatin complex sponge. After crosslinking, the complex sponge was cut into pieces 1 mm diameter x 1 mm high to fit the bone defect area. The amount of fluvastatin in the sponge was adjusted to control (0 nmol), 0.1 nmol, 0.2 nmol, and 0.4 nmol. Using 20-week-old low-turnover osteoporosis model mice (SAMP6) and normal model mice (SAMR1), cylindrical and bone defects were made in sites 1.0 mm in diameter and depth, 1 mm of 3 mm from both sides of the distal end of the femur. The complex sponge was then inserted into each site, and the wound was closed. Radiographic analysis and histologic examinations were then performed. In SAMP6, the bone volumes of the bone defect areas in the 0.1nmol and 0.2nmol groups were significantly higher compared with those of the control and 0.4nmol groups at 14 and 21 days. Histological observation showed that the volume of newly formed bone increased in the 0.1nmol and 0.2nmol groups compared to those in the control and 0.4nmol groups at 14 and 21 days. The bone volumes of newly formed bone in SAMR1 were higher than were those in SAMP6, and the optimum concentration of fluvastatin was different between SAMP6 and SAMR1. The present study suggests that local administration of a fluvastatin-gelatin complex sponge provides improvement in bone healing in low-turnover osteoporosis.