生育三烯酚通过激活Wnt/β-catenin信号减少激素诱导骨质疏松大鼠骨量流失

Tocotrienols reduce bone loss by hormone-induced osteoporosis in rats through activating Wnt/β-catenin signaling

目的观察生育三烯酚对糖皮质激素性骨质疏松(glucocorticoid-induced osteoporosis,GIOP)大鼠骨量影响并探索可能的机制。方法将30只12周龄雄性SD大鼠随机分为3组:对照组(n=10)、地塞米松组(DEX,n=10)及地塞米松+生育三烯酚组(DEX+TTS,n=10)对应给予DEX及TTS干预。12周后取双侧股骨进行微型计算机断层扫描(Micro-CT)和骨生物力学检测。同时检测抗酒石酸酸性磷酸酶(TRACP)、Ⅰ型胶原交联羧基末端肽(CTX-I)、碱性磷酸酶(ALP)和骨钙素(OC)。蛋白印迹检测各组BMP-2、OPG及RANKL蛋白表达改变。结果DEX组大鼠的骨密度(bone mineral density,BMD)、骨显微结构和骨生物力学指标均明显低于对照组(P<0.05)。骨吸收指标(TRACP和CTX-I)升高,骨形成指标(ALP和OC)降低。TTS治疗后骨密度、骨显微结构、骨生物力学指标均有明显改善。与DEX相比,DEX+TTS组的TRACP和CTX-I显著降低,ALP和OC显著升高。蛋白印迹结果表明DEX组的BMP-2和OPG明显降低,而RANKL水平显著上升;TTS治疗后BMP-2和OPG明显上升,而RANKL水平显著降低。结论TTS可以通过降低骨吸收和促进骨形成及激活Wnt/β-catenin信号来提高GIOP大鼠骨密度、骨微观结构和骨强度。

Objective To observe the effect of tocotrienol on bone mass in glucocorticoid-induced osteoporosis(GIOP)rats and to explore the possible mechanisms.Methods Thirty12-week-old male Sprague-Dawley rats were randomly divided into three groups:the control group(n=10),the dexamethasone group(DEX,n=10),and the dexamethasone plus tocotrienol group(DEX+TTS,n=10).DEX and DEX+TTS were administered accordingly.The bilateral femurs were collected after 12 weeks to perform micro-CT and bone biomechanical examinations.Meanwhile,tartrate-resistant acid phosphatase(TRACP),cross-linked carboxy-terminal telopeptide of type I collagen(CTX-I),alkaline phosphatase(ALP),and osteocalcin(OC)were tested.Western blotting(WB)was used to detect the changes of BMP-2,OPG,and RANKL protein expressions in each group.Results Bone mineral density(BMD),bone microstructure,and bone biomechanical indexes in the DEX group were significantly lower than those in the control group(P<0.05).Bone resorption indicators(TRACP and CTX-I)increased and bone formation markers(ALP and OC)decreased.BMD,bone microstructure,and bone biomechanical parameters were significantly improved after TTS treatment.Compared with those in the DEX group,TRACP and CTX-I in the DEX+TTS group were significantly reduced,and ALP and OC were significantly increased.WB result showed that BMP-2 and OPG were significantly decreased,while RANKL levels were significantly increased in the DEX group.BMP-2 and OPG were significantly increased,while RANKL levels were significantly decreased after TTS treatment.Conclusion TTS increases BMD,bone microstructure,and bone strength in GIOP rats by reducing bone resorption and promoting bone formation and activating Wnt/β-catenin signaling.