骨质疏松相关信号通路的研究进展

Research progress of signaling pathways in osteoporosis

骨质疏松症（osteoporosis，OP）是一种以骨量降低，骨组织微结构破坏，导致骨脆性增加、骨强度下降，易发生骨折为特征的全身性代谢退化性骨病，其发生、发展是一个多因素作用、多基因参与、多阶段经历形成的极其复杂的生物学过程。骨质疏松是我国排名第四的慢性病，主要影响绝经后妇女和老年人。骨量是由破骨细胞的骨吸收和成骨细胞增加基质沉积矿化的作用共同维持的，若两者之间发生平衡紊乱，则导致骨形成作用减弱，骨吸收作用增强，骨稳态发生改变，引起骨质疏松。传统治疗骨质疏松的药物或只是抑制骨吸收（双膦酸盐、雌激素等），或只是促进骨形成（甲状旁腺激素、他汀类），或仅补充钙源（钙片）。这种单点局部治疗，对于骨质疏松这一复杂的病变很难奏效。近几年学者研究与骨质疏松有关的分子信号通路，其中丝裂原活化蛋白激酶;（mitogen-activated protein kinase, MAPK）, PI3K/Akt, Wnt/β-catenin,RANKL/RANK/OPG, Hedgehog 和Notch信号通路在骨质疏松发病的分子机制中发挥重要调节作用。此外，与骨质疏松相关的还有GH／IGF-1、PPAR-γ、PTH信号通路。虽然以这些信号通路为作用靶点是研究开发新型抗骨质疏松药物或预防骨质疏松发生的新策略，但骨质疏松相关信号通路间存在交互或交叉作用，发病机制复杂，使得治疗更加困难。因此，本文通过对OP相关信号通路进行综述，旨在探讨OP形成的分子机制，以进一步深入研究新的作用靶点，获得更加安全、有效的抗骨质疏松药物。

Osteoporosis is a systemic metabolic degenerative skeletal disease, characterized by reduced bone mass and disrupted bone microarchitecture, leading to enhanced bone fragility, decreased bone strength and increased susceptibility to frac- tures. Its occurrence and development is an extremely complex biological process, which is a multi factor, multi gene and multi stage experience. Osteoporosis is the fourth chronic disease in our country, which mainly affects postmenopausal women and the el- derly. Bone mass is jointly maintained by the action of bone resorption by osteoclasts and bone formation by osteoblasts. If the im- balance between the two occurs, resulting in reduced bone formation and increased bone resorption, bone homeostasis is changed to cause osteoporosis. Traditional treatment for osteoporosis are drugs which just to depress bone resorption （such as bisphospho- nates and estrogen）, or just to promote bone formation （such as PTH and statins）, or just to supply the source of calcium. This sin- gle point of local treatment is clearly difficult to play a long-term part in complex lesions of osteoporosis. In recent years, research- ers have studied the molecular signaling pathways related to osteoporosis. The current studies reveal that signaling pathways in os- teoporosis include MAPK, PI3K/Akt, Wnt/β-catenin, RANKL/RANK/OPG, Hedgehog and Notch signaling pathways. These signal- ing pathways play an important role in the molecular pathogenesis of osteoporosis. In addition, there are GH/IGF- 1, PPAR-γ, PTH signaling pathways and so on. Taking these signaling pathways as targeting points is a new strategy for the development of new anti osteoporosis drugs or the prevention of osteoporosis. But there are cross-talks and/or interactions between these signaling pathways related to osteoporosis and the pathogenesis of osteoporosiswhich make its therapy more difficult. This paper reviews the research progress of signaling pathway in osteoporosis in order to explore the molecular mechanism of its occurrence. Thus these signaling pathways can be taken as new targets to develop safer and more effective anti-osteoporosis drugs.