Psoralen stimulates osteoblast differentiation through activation of BMP signaling.
Psoralen stimulates osteoblast differentiation through activation of BMP signaling.
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DOI：
10.1016/j.bbrc.2011.01.021
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发表时间：
2011-02-11
影响因子：
3.1
通讯作者：
Wang YJ
中科院分区：
文献类型：
--
作者：
Tang DZ;Yang F;Yang Z;Huang J;Shi Q;Chen D;Wang YJ
骨质疏松症是一种全身性骨骼疾病，其特征在于低骨量和骨组织的微结构退化，从而增加骨脆性和骨折易感性。为了改善骨质疏松症的治疗，非常需要鉴定具有最小副作用的合成代谢和口服药物。补骨脂素是一种从中草药中提取的香豆素类衍生物，数千年来一直用于治疗骨骼疾病。然而，补骨脂素在成骨细胞功能中的作用及其潜在的分子机制仍然知之甚少。在这项研究中，我们发现，Peglien促进成骨细胞分化的原代小鼠颅骨成骨细胞的剂量依赖性的方式，表现为成骨细胞特异性标志基因的表达上调，包括I型胶原，骨钙素和骨唾液酸蛋白和碱性磷酸酶活性的增强。我们进一步证明，Pdifen以剂量依赖的方式上调Bmp 2和Bmp 4基因的表达，增加磷酸化Smad 1/5/8的蛋白水平，并激活BMP报告基因（12 xSBE-OC-Luc）活性，以及增强BMP信号传导的直接靶基因Osx的表达。Bmp 2和Bmp 4基因的缺失消除了Peptien对成骨细胞标志基因Col 1、Alp、Oc和Bsp表达的刺激作用。我们的研究结果表明，补骨脂素通过激活BMP信号传导来促进成骨细胞分化，并表明补骨脂素可能是一种潜在的合成代谢剂，用于治疗骨质疏松症等骨丢失相关疾病的患者。
Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture. In order to improve the treatment of osteoporosis, identification of anabolic and orally available agents with minimal side effects is highly desirable. Psoralen is a coumarin-like derivative extracted from Chinese herbs, which have been used to treat bone diseases for thousands of years. However, the role of Psoralen in osteoblast function and the underlying molecular mechanisms remain poorly understood. In this study, we found that Psoralen promoted osteoblast differentiation in primary mouse calvarial osteoblasts in a dose-dependent manner, demonstrated by up-regulation of expressions of osteoblast-specific marker genes including type I collagen, osteocalcin and bone sialoprotein and enhancement of alkaline phosphatase activity. We further demonstrated that Psoralen up-regulated the expression of Bmp2 and Bmp4 genes, increased the protein level of phospho-Smad1/5/8, and activated BMP reporter (12xSBE-OC-Luc) activity in a dose-dependent manner, as well as enhanced the expression of Osx, the direct target gene of BMP signaling. Deletion of the Bmp2 and Bmp4 genes abolished the stimulatory effect of Psoralen on expression of osteoblast marker genes, such as Col1, Alp, Oc and Bsp. Our results suggest that Psoralen acts through activation of BMP signaling to promote osteoblast differentiation and demonstrate that Psoralen could be a potential anabolic agent to treat patients with bone loss-associated diseases such as osteoporosis.
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影响因子：
9.8
作者：
Styrkarsdottir U;Cazier JB;Kong A;Rolfsson O;Larsen H;Bjarnadottir E;Johannsdottir VD;Sigurdardottir MS;Bagger Y;Christiansen C;Reynisdottir I;Grant SF;Jonasson K;Frigge ML;Gulcher JR;Sigurdsson G;Stefansson K
通讯作者：
Stefansson K
影响因子：
7.2
作者：
Wong, R. W. K.;Rabie, A. B. M.
通讯作者：
Rabie, A. B. M.
影响因子：
56.9
作者：
Mundy, G;Garrett, R;Gutierrez, G
通讯作者：
Gutierrez, G
影响因子：
5.3
作者：
Zhao, Ming;Qiao, Mei;Mundy, Gregory R.
通讯作者：
Mundy, Gregory R.
影响因子：
5.3
作者：
Zhao, Ming;Ko, Seon-Yle;Mundy, Gregory R.
通讯作者：
Mundy, Gregory R.