核心结合因子beta在骨折愈合中作用及机制研究

Mesenchymal stem cell can differentiate into osteoblast and become mature, which play important role in bone fracture healing. Core binding factor alpha 1 (Cbfa1, Runx2) plays a central role in osteoblastogenesis, Cbfb can enhance Runx2’s ability of binding to DNA, and accelerate MSC differentiate into osteoblast. Cbfb knock out mice die after birth because of serious defect of bone formation. We builded a Cbfb knock out mice model which can grow mature using conditional knock out system, and found that Cbfb can regulate chondrocyte and osteoblast differentiation. Runx2 overexpression can promote BMSC differentiate into osteoblast and accelerate bone fracture healing, and we deduce that Cbfb also plays important role in bone fracture healing. To study Cbfb’s function in bone healing, we will build bone fracture model, transplant Cbfb-overexpression MSC using lentivirus transfection system, and study its impact in MSC differentiation、bone healing and the signal pathway in vivo and in vitro, by molecular biology technique and bone mass detection. This project will make new ideas in the molecular mechanism of MSC differentiation and bone healing, and may help us to find new methold of bone fracture healing.

间充质干细胞（MSC）向成骨细胞分化及成熟在骨折愈合中起着重要作用。核心结合因子a1（Cbfa1，Runx2）在成骨分化中起核心调控作用， Cbfb能提高Runx2的DNA结合能力，促进MSC向成骨细胞分化并促其成熟。Cbfb敲除小鼠骨发育严重障碍而在出生后死亡，申请者利用特异性敲除系统，构建了可以发育成熟的Cbfb敲除动物模型，发现Cbfb可以调节软骨细胞、成骨细胞分化成熟。Runx2高表达能促进BMSC成骨分化并达到骨愈合，我们推测Cbfb在骨折愈合中也发挥着重要作用。为了研究Cbfb在骨折愈合中的作用，本课题将建造骨折模型，利用慢病毒转染系统提高MSC中Cbfb的表达并移植至骨折处，采用分子生物学、检测骨量形成等技术，在体外、体内环境中研究Cbfb对MSC分化、骨折愈合的影响及其作用机制。本课题将从新的方向阐明MSC分化及骨折愈合的机制，并为研究促进骨折愈合新方法提供思路。