糖皮质激素性骨质疏松（GIOP）是由于糖皮质激素拮抗Wnt信号造成破骨、成骨细胞失衡，现有治疗未能同时调控多种靶细胞，临床上亟需发掘更有效的治疗方式。前期申请人报道：齿龈间充质干细胞（GMSC）可通过调节免疫并抑制破骨细胞来治疗免疫性关节炎。申请人也发现GMSC可治疗原发性骨质疏松，但MSC的功能异质性限制其转化。我们通过单细胞测序发现GMSC中存在CD39+亚群，其可更好的抑制T细胞增殖和破骨细胞分化并促进成骨，同时高表达Wnt信号。因此，我们推测CD39+亚群拥有更强的骨免疫调控功能，对GIOP有着更佳的治疗效果，其调控能力与Wnt信号有关。本项目拟采用小鼠GIOP模型，运用流式分选、shRNA转染等手段探究CD39+GMSC在体内外通过调节骨免疫治疗GIOP的机制。本课题研究将为临床上GIOP的治疗找到新的突破口，为其干细胞治疗奠定基础，为筛选强效亚群MSC的临床应用提供思路。

Glucocorticoids-induced osteoporosis (GIOP) is caused by glucocorticoids antagonizing Wnt signaling, resulting in an imbalance of osteoclasts and osteoblasts. Existing treatments fail to regulate multiple target cells at the same time, so it is urgent to find more effective treatment. Applicant has previously reported that Gingival Mesenchymal Stem Cells (GMSC) can treat autoimmune arthritis by suppressing osteoclasts. Applicant has also discovered that GMSC can treat primary osteoporosis, but the functional heterogeneity of MSC limits its clinical transformation. Based on single cell sequence properties, we found that the presence of CD39+ subpopulation in GMSC, which can better inhibit T cells proliferation, suppress osteoclasts differentiation and promote osteogenesis, with a high expression of Wnt signals. Therefore, we speculated that the CD39+ subset has stronger bone immunomodulatory functions and better therapeutic effects on GIOP, and its regulation ability is related to Wnt signaling. This project intends to use the GIOP mouse model, using flow sorting, shRNA transfection and other methods to verify the therapeutic effect of CD39+ GMSC on GIOP through bone immunomodulatory in vitro and in vivo. The research on this topic will find a new breakthrough in the clinical treatment of GIOP, laying the foundation for its stem cell therapy, and providing ideas for the clinical application of screening powerful MSC subsets.