Osteomacs高表达FOXA2对破骨细胞分化的作用和机制研究

Osteomacs是最新发现的一个巨噬细胞亚群，已被证明与骨代谢密切相关。然而，截至目前，其在骨质疏松（OP）中的作用及分子机制仍不清楚，尤其是其对破骨细胞分化的调控研究仍为空白。我们前期研究发现：OP小鼠骨髓中Osteomacs的数量显著增加，且在小鼠体内剔除部分Osteomacs可有效缓解OP骨丢失。进一步研究显示：FOXA2在Osteomacs中特征性高表达，而以siRNA敲降Osteomacs的FOXA2表达可明显抑制破骨细胞的过度激活。据此我们推测：FOXA2可能是Osteomacs发挥骨稳态调控作用的分子基础，参与OP的发生和进展。后续，本项目拟进一步采用临床标本、多模式OP模型、转录组学、骨靶向腺相关病毒实验等手段深入研究Osteomacs高表达的FOXA2基因在调控破骨细胞分化和骨丢失中的作用和分子机制，为OP的防治提供新的靶点和思路。

Osteomacs is a newly discovered subgroup of macrophages, which has been shown to be closely related to bone metabolism. However, up to now, its role in osteoporosis (OP) and its molecular mechanism are still unclear, especially its regulation of osteoclast differentiation is still blank. Our previous research found that the number of Osteomacs in the bone marrow of OP mice increased significantly, and removing some Osteomacs from the mice could effectively alleviate OP bone loss. Further studies have shown that FOXA2 is characteristically highly expressed in Osteomacs, and knocking down the FOXA2 expression of Osteomacs with siRNA can significantly inhibit the excessive activation of osteoclasts. Based on this, we speculate that FOXA2 may be the molecular basis for Osteomacs to regulate bone homeostasis and participate in the occurrence and progression of OP. In the follow-up, this project intends to further use clinical specimens, multimodal OP models, transcriptomics, bone-targeting adeno-associated virus experiments and other methods to in-depth study the role and molecule of the FOXA2 gene highly expressed by Osteomacs in regulating osteoclast differentiation and bone loss The mechanism provides new targets and ideas for the prevention and treatment of OP.