LIF依赖的骨质疏松调控机制——铁累积和SOST的双重作用

骨质疏松症作为一种常见疾病，与牙槽骨吸收及修复重建关系密切。近年来的研究发现铁是影响成骨破骨平衡的危险因子。铁累积不但可单独诱发骨质疏松，且可与性激素水平变化共同影响骨质疏松症的发展。目前对铁累积的调控机制尚不清楚，在前一项自然科学基金的研究中，我们意外发现基因敲除白血病抑制因子（LIF）导致牙齿颜色变白，追究原因发现是由于LIF敲除导致体内铁累积，并且发现LIF对重要的铁代谢调节因子——铁调素具有调控作用。此外，骨硬化蛋白（SOST）抗体已在2019年成为治疗骨质疏松的药物，而LIF对骨细胞表达SOST有抑制作用。因此我们提出LIF可以通过特定信号通路对铁代谢进行调节，降低血铁浓度，并抑制骨细胞表达骨硬化蛋白，调节骨形成与骨吸收之间的平衡，从而减缓骨质疏松的发展。

As a common disease, osteoporosis is closely related to alveolar bone absorption and reconstruction. In recent years, iron stores could be an independent risk factor for the balance between osteogenesis of osteoblast and bone resorption of osteoclast. Iron overload could not only induce osteoporosis but also affect the severity of osteoporosis with hormone concentration. So far, the regulation mechanism of iron stores remains to be proven. In our previous foundation, we surprisingly found that lack of leukemia inhibitory factor (LIF) leads to the chalky white of incisor which due to the abnormal iron stores. Furthermore, hepcidin, a key factor to iron metabolism, is regulated by LIF. Besides, a monoclonal antibody of sclerostin (SOST) has been approved to be an effective treatment of osteoporosis. And the SOST expressed by osteocyte is inhibited by LIF. Thus, combined with the results we found, we proposed that LIF could regulate iron metabolism, decrease serum iron concentration by specific signal pathways and inhibit SOST expression in osteocyte, then rebalance bone formation and bone absorption, consequently slow down the progress of osteoporosis.