补骨脂素对乳鼠颅骨成骨细胞分化成熟的影响

骨质疏松症是一种全身性骨骼疾病,其特点是骨量低、骨微结构恶化、骨脆性增加、易骨折。为了改善骨质疏松,需要寻找合成代谢和口服药物的副作用最小的替代药物。补骨脂素是从中草药中提取的香豆素衍生物。然而,补骨脂素在成骨细胞功能中的作用及其分子机制尚不清楚。本研究发现,补骨脂素通过上调成骨细胞特异性标志基因(包括icollagen,骨钙素和骨唾液蛋白)的表达,增强碱性磷酸酶的活性,以剂量依赖的方式促进小鼠原代成骨细胞的成骨分化。本研究同时证明补骨脂素能上调BMP2和BMP4基因的表达,提高磷酸化smad1/5/8蛋白水平,激活BMP报告基因(12xbe-oc-luc)的活性以及增强BMP信号直接靶基因osx的表达。BMP2和BMP4基因的缺失消除了补骨脂素对成骨细胞标志基因col1、alp、oc和bsp表达的促进作用。结果表明,补骨脂素通过激活BMP信号促进成骨细胞分化,提示补骨脂素可能是治疗骨质疏松等骨丢失相关疾病的一种潜在的合成代谢剂。

Effect of Psoralen on Differentiation and Maturation of Skull Osteoblasts in Suckling Rats

Osteoporosis is a systemic skeletal disease characterized by low bone mass,deterioration of bone microstructures,increased bone fragility and easy fracture.In order to improve the treatment of osteoporosis,there is a great need to identify alternative medicines with minimal side effects from anabolic and oral medications.Psoralen is a coumarin derivative extracted from Chinese herbal medicine.However,the role of Psoralen in osteoblast function and its molecular mechanism are still unclear.In this study,psoralen enhanced the activity of alkaline phosphatase by up-regulating the expression of osteoblast-specific marker genes(including icollagen,osteocalcin and bone salivary protein) and promoted the osteogenic differentiation of primary mouse osteoblasts in a dose-dependent manner.We also demonstrated that psoralen can up-regulate the expression of BMP2 and BMP4 genes,increase the level of phosphorylated smad1/5/8 protein,activate the activity of BMP reporter gene(12 xbeoc-luc) and enhance the expression of osx,the direct target gene of BMP signal.The deletion of BMP2 and BMP4 genes eliminated the effect of psoralen on the expression of osteoblast marker genes col1,alp,oc and bsp.Our results suggested that psoralen promotes osteoblast differentiation by activating BMP signaling,suggesting that psoralen may be a potential metabolite for the treatment of bone loss-related diseases such as osteoporosis.