高盐饮食通过激活破骨细胞促进小鼠骨质疏松发生

Promotion of osteoporosis by high-salt dietary through activation of osteoclasts in mice

目的明确高盐饮食对小鼠破骨细胞分化的影响及其促进骨质疏松的作用。方法获得C57小鼠骨髓单个核细胞,在体外定向诱导破骨分化体系中比较对照组(未加入氯化钠)、低剂量组(20mmol/L氯化钠)及高剂量组(40 mmol/L氯化钠)破骨细胞生成数量;将24只C57小鼠随机平均分为正常组(普通饲料喂养)、卵巢切除组(切除卵巢,普通饲料喂养)、高盐饮食组(切除卵巢,8%高盐饲料+生理盐水喂养),6周后分析3组左侧股骨破骨细胞生成数量并测定血清骨吸收及骨保护指标水平;选择右侧股骨进行显微CT扫描,比较3组骨组织形态计量学参数。结果体外高盐状态破骨细胞生成数量明显增加;体内高盐饮食组破骨细胞生成数量明显高于其它两组,I型胶原羧基端肽和核因子κB受体活化因子配体不同程度增加,骨保护素水平显著降低,骨体积分数、骨皮质厚度、骨小梁数量和骨小梁厚度下降尤为明显,骨表面积/骨体积、骨小梁分离度和骨小梁模式因子不同程度增高。结论高盐饮食可通过激活小鼠破骨细胞分化及其功能活化增强骨吸收作用,进而诱导骨质疏松发生。

Objective To clarify the promotion effect of mouse osteoclast differentiation and osteoporosis by high-salt dietary.Methods Bone marrow mononuclear cells of C57 mice were obtained and induced to differentiate into osteoclasts.During this procedure,cells were cultured in each of 3 kinds of medium:no salt addition(control group),addition of 20 mmol/L salt(low-dose group),and addition of 40 mmol/L salt(high-dose group).The quantity of formed osteoclasts was acquired and compared among all 3 groups.In in-vivo study,a total of 24 C57 mice were divided into 3 groups randomly and equally:a normal group(regular feeding),an ovariectomy group(removal of ovary and regular feeding),and a high-salt group(removal of ovary,fed with 8%salt and drinking normal saline).At 6 weeks after administration,in all 3 cohorts,the number of generated osteoclasts in left femurs,as well as indicators associated with bone resorption and protection in serum were acquired.Moreover,bone histomorphometric parameters in right femurs were obtained and compared between each group using micro-CT.Results High-salt medium ex vitro enhanced the formation of osteoclasts significantly.Similarly,in vivo study found the largest number of osteoclasts in the high-salt group in comparison with the other 2 cohorts.Also in this group,C-telopeptide of type I collagen and receptor activator of nuclear factor-κB ligand increased at different levels,while osteoprotegerin decreased remarkably.With respect to bone histomorphometric parameters in the high-salt group,bone volume/total volume,cortical wall thickness,trabecular number and trabecular thickness were significantly increased whereas bone surface area/bone volume,trabecular spacing and trabecular pattern factor were increased at various levels.Conclusions High-salt dietary enables the occurrence of osteoporosis through activating differentiation of bone marrow mononuclear cells into osteoclasts and strengthening of overall bone-resorption potential.