唑来膦酸胶原膜对骨代谢细胞的影响初探

目的 通过研究唑来膦酸胶原膜对骨代谢细胞的影响,探讨该载药膜是否具有抑制局部骨吸收、促进局部骨形成的能力.方法 分别以双层胶原膜(Bio-Gide(R))和单层胶原膜(BME-10X(R))为载体,吸附不同浓度唑来膦酸(zoledronic acid,ZA),制备唑来膦酸胶原膜,分别命名为BG0、BG1、BG2、BG3组和BM0、BM1、BM2、BM3组(BG代表双层胶原膜,BM代表单层胶原膜,0、1、2、3分别代表唑来膦酸浓度为0、1×10-4、1×10-3、1×10-2 mol/L),设置无胶原膜组为空白对照组.通过离体细胞培养,评价唑来膦酸胶原膜对破骨细胞和成骨细胞的影响.结果 唑来膦酸胶原膜与破骨细胞体外共培养显示:培养第7大,BG1、BG2、BG3、BM1、BM2、BM3组骨吸收陷窝面积百分比分别为18.80%、14.75%、14.28%、20.51%、15.77%、15.12%,明显低于BG0(31.53%)和BM0(32.22%,P＜0.05),载药量越高,其抑制效果越强.唑来膦酸胶原膜与成骨细胞体外共培养显示:培养第7天,BG2组增殖指数(7.00)明显高于BG0(6.90);培养第4天,BG2、BG3、BM2、BM3组碱性磷酸酶表达(分别为154.67、154.33、155.33、152.00 U/g)明显高于BG0(129.33 U/g)和BM0(127.67 U/g,P＜0.05).结论 唑来膦酸胶原膜可同时具有抑制骨吸收和促进成骨细胞增殖的能力.

Abstract：

Objective To develop zoledronic acid (ZA)-loaded collagen membranes, and to study its effect on osteoclast and osteoblast so as to investigate whether ZA-loaded membranes can inhibit local bone resorption and promote bone formation. Methods ZA-loaded double-layer (Bio-Gide(R)) and singlelayer(BME-10X(R)) collagen membranes were prepared and divided into eight groups according to the concentrations of ZA in the membrane, namely Group BG0, BG1, BG2, BG3 and BM0, BM1, BM2, BM3 (BG refers to Bio-Gide(R), BM refers to BME-10X(R), 0, 1,2, 3 refer to the concentrations of ZA, 0, 1 ×10-4, 1 × 10-3, 1 × 10-2 mol/L respectively). Blank control group was set without using collagen membrane. The effects of ZA-loaded membranes on osteoclast and osteoblast were assessed using in vitro cell culture models. Results In vitro coculture of ZA-loaded membrane with osteoclast for seven days showed that the percentage of bone resorption area in BG1, BG2, BG3, BM1, BM2, BM3 were 18.80%,14.75%, 14.28%, 20.51%, 15.77%, 15.12% respectively, which were lower than that in BG0 (31.53%) and BM0(32.22%, P ＜0.05), and the higher ZA loading was, the stronger its inhibition to osteoclast was. In vitro coculture of ZA-loaded membrane with osteoblast for four days indicated that alkaline pbosphatase(ALP) activities in BG2 (154.67 U/g), BM2 (154.33 U/g), BG3 (155.33 U/g), BM3 (152.00 U/g) were higher than that in BG0(129.33 U/g) and BM0(127.67 U/g, P ＜ 0.05). What's more, results from seven-day coculture showed that proliferation index in BG2(7.00) was higher than that in BG0(6.90). Conclusions ZA-loaded collagen membrane can not only inhibit osteoclastic bone resorption but also improve proliferation of osteoblast.

Study on the effects of zoledronic-acid-loaded collagen membrane on bone metabolism cells

Objective To develop zoledronic acid (ZA)-loaded collagen membranes, and to study its effect on osteoclast and osteoblast so as to investigate whether ZA-loaded membranes can inhibit local bone resorption and promote bone formation. Methods ZA-loaded double-layer (Bio-Gide(R)) and singlelayer(BME-10X(R)) collagen membranes were prepared and divided into eight groups according to the concentrations of ZA in the membrane, namely Group BG0, BG1, BG2, BG3 and BM0, BM1, BM2, BM3 (BG refers to Bio-Gide(R), BM refers to BME-10X(R), 0, 1,2, 3 refer to the concentrations of ZA, 0, 1 ×10-4, 1 × 10-3, 1 × 10-2 mol/L respectively). Blank control group was set without using collagen membrane. The effects of ZA-loaded membranes on osteoclast and osteoblast were assessed using in vitro cell culture models. Results In vitro coculture of ZA-loaded membrane with osteoclast for seven days showed that the percentage of bone resorption area in BG1, BG2, BG3, BM1, BM2, BM3 were 18.80%,14.75%, 14.28%, 20.51%, 15.77%, 15.12% respectively, which were lower than that in BG0 (31.53%) and BM0(32.22%, P ＜0.05), and the higher ZA loading was, the stronger its inhibition to osteoclast was. In vitro coculture of ZA-loaded membrane with osteoblast for four days indicated that alkaline pbosphatase(ALP) activities in BG2 (154.67 U/g), BM2 (154.33 U/g), BG3 (155.33 U/g), BM3 (152.00 U/g) were higher than that in BG0(129.33 U/g) and BM0(127.67 U/g, P ＜ 0.05). What's more, results from seven-day coculture showed that proliferation index in BG2(7.00) was higher than that in BG0(6.90). Conclusions ZA-loaded collagen membrane can not only inhibit osteoclastic bone resorption but also improve proliferation of osteoblast.