NFATc1在骨质疏松症中的研究进展

Research advances of NFATc1 in osteoporosis

骨重塑过程不平衡是骨质疏松症发生的重要机制之一,其主要是由于破骨细胞对骨的重吸收超过了成骨细胞介导的骨形成。NFATc1被证实参与了调控骨吸收过程。笔者综述了NFATc1在破骨细胞中调控的信号通路与分子机制,拟为骨质疏松症提供新的治疗思路和潜在的治疗靶点。并得出以下结论:①当骨吸收过程中破骨细胞的介入程度超过成骨细胞的介入程度时,从而导致骨重塑过程失去平衡,而骨质疏松症则将持续发展;②NFATc1在破骨细胞吸收过程中的关键转录调控是通过RANKL-RANK、NF-κB、MAPK和Ca^(2+)信号通路,调控破骨细胞在骨代谢过程中的生成和分化,从而介导破骨细胞过度生成引起的骨形成和骨吸收之间的失衡;③目前抗骨质疏松药物策略并未对该疾病产生非常显著的影响;④关于生物材料靶向NFATc1的研究还处于起步阶段,仍需深入探索。

Imbalanced bone remodeling process is one of the important mechanisms in the development of osteoporosis,which is mainly due to the resorption of bone by osteoclasts exceeding osteoblast-mediated bone formation.NFATc1 has been shown to be involved in regulating the bone resorption process.The article reviews the signaling pathways and molecular mechanisms regulated by NFATc1 in osteoclasts,which are proposed to provide new therapeutic ideas and potential therapeutic targets for osteoporosis.The following conclusion have been obtained:(1)When the intervention of osteoclasts in the process of bone resorption exceeds that of osteoblasts,the imbalance in the process of bone remodeling occurs and osteoporosis may develop.(2)The key transcriptional regulation of NFATc1 in osteoclast resorption is through the RANKL-RANK,NF-κB,MAPK,and Ca^(2+) signaling pathways,which regulate osteoclast generation and differentiation during bone metabolism,thereby mediating the imbalance between bone formation and bone resorption induced by osteoclast overgeneration.(3)The current anti-osteoporosis drug strategy does not have a very significant impact on the disease.(4)The research on the targeting of biomaterials to NFATc1 is in the initial stage and still needs to be explored thoroughly.