RUNX1是一种与造血系统发生密切相关的转录因子,其基因突变在血液系统肿瘤,特别是在急性髓系白血病的发生发展中起到重要的致病作用。近年来研究表明,RUNX1也参与调控骨发育以及骨相关疾病的病理进程。RUNX1能促进间充质干细胞向软骨细胞及成骨细胞分化,并调控软骨细胞成熟及细胞外基质的形成。RUNX1在间充质干细胞、软骨细胞及成骨细胞中的表达对于维持正常的骨发育和骨质与骨量有着重要意义。RUNX1还能抑制破骨细胞的分化及功能,且该过程可能存在性别二态性。此外,通过基因敲除鼠模型还阐明了RUNX1缺乏在骨关节炎、骨折愈合延迟、骨质疏松等病理状况中的促病机制。然而,RUNX1在调控软骨细胞肥大分化、调控破骨细胞功能中的性别二态性,以及在糖尿病、衰老、感染及慢性炎症等相关骨丢失中的作用等方面还尚不完全清楚。本综述系统总结了关于RUNX1在骨生物学领域中的研究进展,为RUNX1作为治疗骨相关疾病,特别是骨关节炎、骨折延迟愈合及骨质疏松的潜在靶点提供思路。
Runt-related transcription factor (RUNX1) is a transcription factor closely involved in hematopoiesis. RUNX1 gene mutation plays an essential pathogenic role in the initiation and development of hematological tumors, especially in acute myeloid leukemia. Recent studies have shown that RUNX1 is also involved in the regulation of bone development and the pathological progression of bone-related diseases. RUNX1 promotes the differentiation of mesenchymal stem cells into chondrocytes and osteoblasts and modulates the maturation and extracellular matrix formation of chondrocytes. The expression of RUNX1 in mesenchymal stem cells, chondrocytes, and osteoblasts is of great significance for maintaining normal bone development and the mass and quality of bones. RUNX1 also inhibits the differentiation and bone resorptive activities of osteoclasts, which may be influenced by sexual dimorphism. In addition, RUNX1 deficiency contributes to the pathogenesis of osteoarthritis, delayed fracture healing, and osteoporosis, which was revealed by the RUNX1 conditional knockout modeling in mice. However, the roles of RUNX1 in regulating the hypertrophic differentiation of chondrocytes, the sexual dimorphism of activities of osteoclasts, as well as bone loss in diabetes mellitus, senescence, infection, chronic inflammation, etc, are still not fully understood. This review provides a systematic summary of the research progress concerning RUNX1 in the field of bone biology, offering new ideas for using RUNX1 as a potential target for bone related diseases, especially osteoarthritis, delayed fracture healing, and osteoporosis.