CAJ | 학술논문

目的利用骨保护蛋白(osteoprotegerin,OPG)基因剔除小鼠模型研究选择性雌激素受体调节剂雷洛昔芬对雌鼠和雄鼠的抗骨质疏松作用.方法取二月龄OPG基因剔除(OPG-/-)的雌鼠和雄鼠各20只.随机分为雷洛昔芬组(3 mg·kg-1·d-1)和安慰剂组,另取野生犁雌鼠10只作为对照组,1个月后杀鼠取材.测量骨密度、骨生物力学、骨形态计量学,并进行骨组织病理学检查及破骨细胞染色,评价雷洛昔芬的疗效.结果 OPG-/-小鼠呈现明显的骨质疏松表型.雷洛昔芬组的雌鼠较安慰剂组腰椎、股骨骨密度明显增高(均P<0.05);骨生物力学结果显示腰椎和股骨最大载荷(P<0.05或P<0.01),弹性模鼍(P<0.05或P<0.01),结构韧性(均P<0.01)均增高,提示骨折风险性下降;破骨细胞染色示腰椎和股骨破骨细胞面积明显减少(均P<0.01);HE染色示骨小梁数目增加,连接性上升;骨形态计量学结果显示骨形成率降低(P<0.05).雷洛昔芬组的雄鼠与安慰剂组相比较无上述改变.结论选择性雌激素受体调节剂雷洛昔芬在OPG基因缺失的情况下仍可改善雌鼠骨质疏松,其作用不完全依赖于OPG基因.雷洛昔芬对OPG-/-雄鼠无效.
목적 이용골보호단백(osteoprotegerin,OPG)기인척제소서모형연구선택성자격소수체조절제뢰락석분대자서화웅서적항골질소송작용.방법 취이월령OPG기인척제(OPG-/-)적자서화웅서각20지.수궤분위뢰락석분조(3 mg·kg-1·d-1)화안위제조,령취야생리자서10지작위대조조,1개월후살서취재.측량골밀도、골생물역학、골형태계량학,병진행골조직병이학검사급파골세포염색,평개뢰락석분적료효.결과 OPG-/-소서정현명현적골질소송표형.뢰락석분조적자서교안위제조요추、고골골밀도명현증고(균P<0.05);골생물역학결과현시요추화고골최대재하(P<0.05혹P<0.01),탄성모타(P<0.05혹P<0.01),결구인성(균P<0.01)균증고,제시골절풍험성하강;파골세포염색시요추화고골파골세포면적명현감소(균P<0.01);HE염색시골소량수목증가,련접성상승;골형태계량학결과현시골형성솔강저(P<0.05).뢰락석분조적웅서여안위제조상비교무상술개변.결론 선택성자격소수체조절제뢰락석분재OPG기인결실적정황하잉가개선자서골질소송,기작용불완전의뢰우OPG기인.뢰락석분대OPG-/-웅서무효.
Objective To observe the effect of raloxifene, a selective estrogen receptor modulator, on osteoporosis in the osteoprotegerin (OPG) gene knock-out female and male mice. Methods Two groups of OPG gene deficient (OPG-/-) female and male mice, 20 mice in each group, were assigned to raloxifene-treated (3 mg The effect of raloxifene was evaluated by comparing the values of bone mineral density (BMD) , bone strength,histomorphometric measurement and osteoclast number between the raloxifene treated group and placebo group.Results As compared with placebo group osteoporotic manifestations were improved in OPG-/- female mice treated with raloxifene orally. BMD was increased both in lumbar vertebrae (P<0.05) and femurs (P<0.01).Bone strength was measured in femurs by three-point bending test and vertebrae by stress test. Results showed that ultimate load, ultimate stress and Young's modulus were increased both at lumbar and femur bone, suggesting decreased risk of fracture. Tartrate-resistant acid phosphatase, a marker enzyme of osteoclasts, was detected, and the number of osteoclasts declined significantly after the treatment of raloxifene. At the same time, results of histomorphometric measurements indicated that bone trabecular volume was increased and bone formation rate decreased from(8.05±4.02)mm3·mm-2·year-1 to (5.48±1.89)mm3·mm-2· year-1(P＜0.05).These findings were found in the group of OPG-/- female mice treated with reloxifene but not in male mice. Conclusions Raloxifene is effective in treating osteoporosis in female OPG-/- mice, indicating that its action is at least in part independent of OPG gene. But it is ineffective in male OPG-/- mice.