线粒体途径相关信号通路对成骨细胞凋亡的作用

The effect of mitochondrial-related signaling pathway on apoptosis of osteoblasts

骨质疏松症是由于多种原因导致的骨质量和骨密度下降,骨微结构遭到破坏,造成骨脆性增加,从而容易发生骨折的一种全身性代谢性骨病变。其中,成骨细胞是促进骨形成的主要功能细胞,是骨质疏松发生的关键细胞,其功能退变和异常凋亡将会引起骨量丢失,诱导骨质疏松发生。因此,探究成骨细胞的凋亡机制对预防和治疗骨质疏松症具有重要意义。其中,线粒体途径是成骨细胞凋亡的主要途径,是由多基因参与、多通路相互作用而形成的复杂过程。因此,本文综述了线粒体途径的凋亡过程及其众多相关信号通路:PI3k/Akt信号通路、MAPK信号通路、Ca^(2+)/CaM信号通路以及其他信号通路和因子(Keap1/Nrf2信号通路、PHB、FoxO家族、cAMP/CREB),同时还归纳了这些信号通路在成骨细胞经线粒体途径凋亡的过程中发挥的促进或者抑制作用,以及他们在成骨细胞凋亡中的一些相互作用。这为进一步探究成骨细胞的凋亡机制和骨质疏松的发病机制提供了可靠依据,也为更深入研究安全、有效的抗骨质疏松药物提供了一些可能的作用靶点(如:Akt、ERK、JNK、p38、Ca^(2+)、PHB、FoxO3a、CREB、Keap1/Nrf2等)。

Osteoporosis is a type of systemic metabolic bone lesion that is prone to bone fractures due to various causes of decreased bone mass and bone density, destruction of bone microarchitecture, and increase of bone fragility. Osteoblasts are the main functional cells that promote bone formation and are the key cells for the development of osteoporosis. Degeneration of osteoblasts and abnormal apoptosis cause bone loss and induce osteoporosis. Therefore, exploring the apoptotic mechanism of osteoblasts is of great significance for the prevention and treatment of osteoporosis. The mitochondrial pathway is the main pathway of osteoblast apoptosis and is a complex process that is formed by the participation of multiple genes and multiple pathways. Therefore, this article reviews the mitochondrial pathway of apoptosis and its many related signaling pathways: PI3k/Akt signaling pathway, MAPK signaling pathway, Ca2+/CaM signaling pathway, and other signaling pathways and factors (Keap1/Nrf2 signaling pathway, PHB, FoxO family, cAMP/CREB). The promotion or inhibition of these signaling pathways in the process of osteoblast apoptosis through the mitochondrial pathway, and some of their interactions in osteoblast apoptosis, are also reviewed. This provide a reliable basis for further exploration of the apoptotic mechanism of osteoblasts and the pathogenesis of osteoporosis, as well as provide some possible targets for a more in-depth study of the safety and efficacy anti-osteoporosis drugs (e.g., Akt, ERK, JNK, p38, Ca2+, PHB, FoxO3a, CREB, Keap1/Nrf2, etc.).